"His policies have made the recession deeper and his policies have made the recovery more tepid," he said, despite a declining unemployment rate and the creation of 200,000 jobs last month.
Over the course of the 90-minute debate, there were plenty of attacks as the former Massachusetts governor's five rivals vied to emerge as his principal rival in the primaries ahead.
Romney won an eight-vote victory in the Iowa caucuses Tuesday, and is far ahead in the pre-primary polls in New Hampshire.
Romney has led in New Hampshire polls for months.
Romney, who often touts his business background, was attacked in the opening moments of the debate.
Rick Santorum went first, dismissing Romney as a mere manager. "Being a president is not a CEO. You've got to lead and inspire," he said.
Unruffled, Romney retorted that a company he once led had created 100,000 jobs on balance, and that a businessman's experience was far better to fix the economy that a lifetime spent in Washington, D.C.
"I'm very proud of the fact that the two enterprises I led were successful," he said, referring to Bain and another firm.
However, the bottom line remains unknown about how many jobs were gained or lost from Romney's work at the Bain Capital private equity company.
Debates can have unforeseen impact. Just days before the New Hampshire primary in 2008, Democratic candidate Barack Obama used that venue to call rival Hillary Rodham Clinton "likable enough" - a dismissive comment that didn't sit well with her supporters.
Obama, who had a significant lead in polls, lost the New Hampshire primary.
Romney's rivals have a sizable gap to close in New Hampshire. Two separate surveys out Friday show him up 20 percentage points or more over his closest rival, Texas Rep. Ron Paul.
Saturday night's debate aired live on ABC and was moderated by news anchors Diane Sawyer and George Stephanopoulos.
The South Carolina primary is on Jan. 21
The Associated Press contributed to this report.