In short, big changes and a Biden presidency instantly having to play defense.
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Senate Republicans, unlike their House counterparts, have not put out a 'contract' or plan for what they would do if they take over, but in speeches and interviews and looking at who is poised to take the gavels at powerful Senate committees, some priorities seem clear.
For starters, inflation.
Laying the blame for historically high inflation at the feet of President Joe Biden and his unified Democratic government, Republicans have repeatedly called for an end to the "spending spree" in Washington.
It's worth noting that some of that increased spending was related to trying to bring the U.S. economy back from a historic pandemic, action that began under former President Donald Trump. Still, Republicans have charged that Democrats went entirely too far with the American Rescue Plan that pumped nearly $2 trillion into the economy, fueling inflation already aggravated by the roiling supply chain crisis.
The situation was made worse with Russian President Vladimir Putin's war in Ukraine.
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Republicans have pointed to a handful of solutions, such as making some of the business tax cuts from their 2017 package -- set to expire in the next few years -- permanent, as well as, mounting an effort to roll back the new corporate minimum tax against larger corporations enacted in the recently-passed climate, health and tax bill by Democrats.
The boogeyman in many GOP ads the latter part of this midterm cycle has been the Democrats' plan to beef up the IRS to go after tax cheats. It was a key way they planned to raise revenue to pay for their climate and health bill, but Republicans seized on it to falsely warn Americans that an "army of IRS agents" were coming for them.
The IRS commissioner, Charles Rettig, a Trump appointee, has tried to reassure lawmakers that the new resources would not be focused on middle income Americans, but the claims continued and oversight hearings are a sure bet. Republicans might even try to find a way to roll back that effort.
Whether or not any of this could have any effect on inflation remains to be seen. Usually tax cuts -- in other words, less revenue for the federal government -- are not seen as inflation-reducing. And while spending cuts are, the level of draconian cuts needed to make a dent are not likely to be approved by a majority of the new majority.
'Drill, baby drill'
With gas prices soaring, Republicans laid into Democrats for clamping down on domestic energy production, and with Wyoming Sen. John Barrasso expected to resume the chairmanship of the Energy Committee, the focus almost surely will be squarely placed on that issue.
In that same vein, and with GOP anger at Sen. Joe Manchin, D-W.Va. for that deal he made with Democrats passing the Inflation Reduction Act having subsided, it is entirely possible that energy permitting reform will be back on the table but in a bipartisan way this time. That is actually something that might get done in the lame duck session.
Investigations ramp up
While Senate Republicans might not ramp up the number of investigations expected by their GOP counterparts in the House, the upper chamber's new majority is expected to spin up quite a few of their own.
For starters, Sen. Chuck Grassley, R-Iowa, who can be is expected to retake the gavel at the Judiciary Committee for a year, has already been looking into the affairs of the president's first son and conservative lightning rod, Hunter Biden. His partner in the years-long effort, Wisconsin Sen. Ron Johnson -- who has been locked in a fierce contest to keep his seat -- can be is expected to helm the powerful investigative subcommittee of the Senate Homeland Security and Governmental Affairs Committee known as the Permanent Subcommittee on Investigations (PSI). It has a large budget for investigative staff, as well as subpoena power
It's unclear if the GOP duo can outrun the Justice Department on this one, though. Federal investigators have made clear they feel they have enough to charge the Hunter Biden with financial crimes, sources told ABC News in early October, and a federal probe has been underway for quite some time.
Top of Grassley's to-do list is also how to tackle the nation's rising violent crime, a centerpiece of GOP campaigns this midterm season, and what to do about what conservatives see as a politicized Justice Department.
"All of the things that Republicans have been talking about that aren't really getting a huge amount of attention in the Judiciary Committee will be a focus, particularly violent crime," a GOP committee aide told ABC News.
Paul, Fauci and the origins of COVID
While it might seem as if the COVID-19 pandemic has lost its grip on the nation, conservative Sen. Rand Paul has some old scores to settle.
Paul, on track to win a third term this year, has promised to investigate the origins of the pandemic, a pet issue for the irascible conservative.
"When we take over in November, I will be chairman of a committee and I will have subpoena power," the Kentucky Republican, told those gathered at a campaign event in Smithfield in May, according to an account from the Associated Press. "And we will get to the bottom of where this virus came from."
Running contrary to two previous scientific reports this summer on the origins of the virus pointing to a zoological connection from the Huanan Seafood Market, a recent report by GOP staff on the Senate panel Paul is set to chair, came to a different conclusion. The 35-page interim report concluded that the origin "was most likely the result of a research-related incident," though the document specifically states, "This conclusion is not intended to be dispositive."
The report does not mention anything about motive, as some conservatives have sought to espouse, claiming China may have weaponized a virus, nor does it mention any involvement of the frequent target of Paul's ire, the nation's top infectious disease expert, Dr. Anthony Fauci.
From practically the outset of the pandemic, Paul questioned the power of the virus and government mandates to try to contain it, repeatedly clashing in hearings with Fauci. All of it fed a "fire Fauci" movement in conservative circles. Fauci, who said he plans to retire at the end of Biden's first term, has said he and his family have been the victim of threats.
Paul and his conservative counterparts in the House have all indicated Fauci's retirement will not stop their push to have him testify and deliver documents related to their probes.
Social media platforms a target
Firebrand Sen. Ted Cruz is champing at the bit to take over at the Senate Commerce Committee. The Texas conservative, known to have 2024 presidential ambitions, is sure to capture the spotlight as he takes on social media platforms, a frequent target of his displeasure claiming widespread anti-conservative bias.
On his podcast, "The Verdict," earlier this year, during the frenzied confusion amid billionaire Elon Musk's attempted takeover of Twitter, Cruz said, "I think it is one of the most important moments for free speech in decades. This is a testing moment where Big Tech keeps getting more and more brazen, saying we can control everything you say; we can control everything you hear; we can control everything in your feed; we can control everything you listen to ... suddenly Elon Musk came in and is threatening to tip over the apple cart."
Of course, there is wide-ranging jurisdiction at this panel covering Commerce, Science, and Transportation issues. There are some GOP aides speculating that Cruz will cast a wide net. "'Science' could cover practically anything," one GOP leadership aide said cryptically.
Whereas House Republicans appear poised to make it more difficult to pass future foreign aid for Ukraine, their Senate counterparts are not expected to follow suit -- at least not the vast majority.
In a recent statement, Senate GOP Leader Mitch McConnell -- a full-throated supporter of Ukraine -- said, "The Biden Administration and our allies need to do more to supply the tools Ukraine needs to thwart Russian aggression," even urging that the aid be "expedited."
Taking over at the Armed Services Committee, barring something unforeseen, will be Sen. Roger Wicker of Mississippi, a McConnell ally.
Wicker, who has worn a Ukrainian flag pin on his lapel since Russia invaded, has fought for military equipment and ammunition to be sent, including MiG fighters and HIMARS (High Mobility Artillery Rocket Systems).
In an interview with Gray Television earlier this month, the senator sounded a tone of bipartisanship on Ukraine funding.
"It's a clear distinction between good and evil, between a war criminal who has no respect for the rights of people to people that are fighting for their own homeland," said Wicker.
The southern border
Republicans have been hammering the administration and Democrats for what they say has been a dereliction of duty at the southern border. Many want a return to the hard-line policies under President Donald Trump.
At the Homeland Security and Governmental Affairs Committee, which has jurisdiction over border issues, the expected chairman, Sen. James Lankford, has pushed repeatedly for hearings.
In an April letter, Lankford and his fellow GOP committee members, wrote to the then-chairman Gary Peters, D-Mich., "The Biden Administration's policies are directly contributing to the historic levels of illegal immigration. Administration officials must explain to the American people the rationale for their decisions, and what their plans are to deal with the consequences of their actions."
The group demanded to have Attorney General Merrick Garland, Homeland Security Secretary Alejandro Mayorkas, Customs and Border Protection Commissioner Chris Magnus, and Rochelle Walensky, CDC Director, among others.
That could prove a template for early hearings.
President Biden has seen a record 84 federal judges confirmed to the bench, according to the American Constitution Society, including one historic nominee to the Supreme Court. But once Republicans take over the Judiciary Committee, that pace is sure to slow, the scrutiny to mount.
Depending on how many nominees the panel's current chairman, Dick Durbin of Illinois, can get cleared and on to full floor confirmation in the lame duck session, scores will still be pending.
There are expected to be 57 nominees pending, according to the ACS, a number that has vexed some progressive groups like Demand Justice.
But the issue that already has Democrats and their outside allies up in arms is the prospect of a Supreme Court vacancy in the next year of Biden's presidency, a full year before presidential election season kicks off.
McConnell, who is expected to keep his position in the new Congress, has suddenly gone mum on whether or not he would stick with the normal practice in the Senate of considering Supreme Court nominees for the president of any party.
Vilified by Democrats for refusing to even consider President Barack Obama's replacement for the late Justice Antonin Scalia, claiming it occurred in a presidential election year with Republicans in charge and voters should decide, McConnell has left everyone wondering if he might enact yet another new policy.
Asked by Fox News recently if he would allow consideration of a Supreme Court nomination if a vacancy occurred on his watch as majority leader next year, McConnell demurred.
"I'm not gonna announce what our agenda might be on appointments before we even become the majority. I hope we're in a position to make a decision," said McConnell.
It would have been easy to say yes. It is quite notable that he did not.
Speaking of McConnell, retaining his position as GOP leader would put him at the 15-year mark for his service as a Senate leader, both in the majority and minority. Next year, he will match the record set by the late Sen. Mike Mansfield, D-Mont. It's widely believed the Kentucky Republican is focused on beating that record, making history, after which he might consider stepping aside, though he has made clear he intends to complete his full term as a senator which ends in 2027.
But it won't all be smooth sledding for McConnell. Former President Donald Trump, who could announce a run for re-election soon after the midterms, has chosen to continue his attacks on the Republican leader, recently calling for his impeachment in a radio interview.
There is no mechanism for impeaching a senator and McConnell enjoys wide support in his conference, but it was a clear sign that the anger at the senator - unleashed in force after the GOP leader lambasted the former president for "practically and morally" sparking the January 6 insurrection - is sure to continue, particularly with Trump more in the spotlight.
McConnell has largely chosen to ignore the attacks, though, as is his style, making light of one Trump nickname - "Old Crow" - telling reporters with a grin, "It's my favorite bourbon."