The vice presidential nominee said that without a change in leadership, "why would the next four years be any different from the last four years?"
Ryan blamed President Barack Obama for high unemployment, dispirited Americans and even the closed General Motors plant in Janesville, Wis., that shut down before Mr. Obama took office.
As expected, Ryan blasted the president on the economy while tickers above the hall showed the rising national debt.
Health care was another part of Ryan's fight.
"The greatest care to Medicare is Obamacare, and we're going to stop it," he said. "Mitt Romney and I know the difference between protecting a program and raiding it. Ladies and gentlemen, our nation needs this debate, we want this debate, we will win this debate."
A generation younger than the 65-year-old Mitt Romney, Ryan emphasized their differences as well as their joint commitment to tackle the economy, an evident appeal to younger voters who flocked to Obama's side in 2008.
"There are songs on his iPod which I've heard on the campaign bus - and on many hotel elevators," he said to laughter from the audience.
Ryan worked with his speechwriting team - some longtime aides, others new additions from Romney's Boston headquarter - to find a balance that appealed to voters from in-play states such as Ohio, Florida and Pennsylvania. Economic hardships have hit close to home there and Ryan's roots in Janesville were an effort to connect with working- and middle-class voters who remain skeptical of the vastly wealthy Romney.
"The man who will accept your nomination tomorrow is prayerful and faithful and honorable," Ryan said in his 37-minute speech. "Not only a defender of marriage, he offers an example of marriage at its best. Not only a fine businessman, he's a fine man, worthy of leading this optimistic and good-hearted country."
Look for ongoing reports from David Ono at the Republican National Convention in Tampa, Fla. Eyewitness News will also be at the Democratic National Convention in Charlotte, N.C., in September.
The Associated Press contributed to this report.