"By the time I'm finished speaking tonight, more Americans will have lost their health insurance. Millions will lose it this year," he said. "I will not walk away from these Americans. And neither should the people in this chamber."
Obama acknowledged that there is uncertainty and confusion out there about what the legislation will do, and he took some of the blame for not explaining it more clearly to the American people.
He urged Americans to take another look at his administration's proposal.
"There's a reason why many doctors, nurses, and health care experts who know our system best consider this approach a vast improvement over the status quo," he said. "But if anyone from either party has a better approach that will bring down premiums, bring down the deficit, cover the uninsured, strengthen Medicare for seniors and stop insurance company abuses, let me know."
Noting the partisan rancor that has marked Washington this year, Obama said that there is one thing that both Democrats and Republicans have agreed on: "We all hated the bank bailout. I hated it. You hated it. It was about as popular as a root canal."
He defended the fees he recently proposed on the big Wall Street banks to recoup the money they owe the government.
"Look, I am not interested in punishing banks. I'm interested in protecting our economy," he said.
Obama proposed taking $30 billion of the money repaid by Wall Street banks and directing it to community banks to allow them to lend to small businesses.
"We're collecting from those banks, and we're going to collect all the money that taxpayers lent those banks ... and some of the money paid back should to go Main Street to help people there," Biden said on "GMA."
Some Republicans have decried the president's plan, saying the bank "fee" amounts to a new tax, which could affect lending to consumers.
"I think it's unfortunate when the president decides to scapegoat one small party within the overall crisis that government was a big part of creating," Romney told George Stephanopoulos. "It's a political effort to try and take the heat off his own administration ... and frankly, I don't think populism has ever created a great nation or a strong economy."
A popular president, Obama has spent a year's worth of political capital on what has turned out to be an unpopular agenda. Tonight's address offered a chance for him to outline what he hopes to do in his second year to get the economy back on track and reconnect with Americans.
With Republican victories in recent elections in Virginia, New Jersey and Massachusetts -- Obama won in the 2008 presidential election -- the president's agenda has, to a degree, been rebuked by the voters.
"I have not detected a level of anger and cynicism about the federal government in my lifetime as high as it is today," said Sen. Evan Bayh, D-Ind.
Obama sought to appeal to voters by discussing programs that would help them directly, including nearly doubling the child tax credit, helping with student loans and developing ways to help the job market improve.
The president stressed that his administration cut taxes last year for working families, small businesses, first-time home buyers and Americans paying for college.