Biden also was more aggressive in his demeanor, repeatedly cutting off Ryan and sometimes talking at the same time as his rival to challenge specific comments.
At one point, Ryan told Biden that "I know you're under a lot of duress to make up for lost ground, but I think people would be better served if we don't keep interrupting each other."
Biden responded: "Well, don't take all the four minutes then" in reference to how much time the candidates had to respond to a particular question. Overall, Biden spoke for about a minute more than Ryan during the 90-minute-debate at Centre College in Danville, Kentucky.
Ryan repeatedly sought to focus the debate on the Obama-Biden record of the last four years, arguing the administration's policies hindered economic recovery and weakened the nation's standing and influence in the world.
For his part, Biden tried to frame the election as a choice between differing directions for the country by contending policies of the Romney-Ryan ticket would hurt the middle class and move the nation backward on social issues such as gay rights and abortion.
Unlike Obama last week, Biden made sure to mention Romney's controversial comments secretly recorded at a May fundraiser in which the former Massachusetts governor spoke dismissively of 47% of Americans who he said depend on government benefits and don't pay taxes.
In one of his most effective moments, he gave a passionate defense of Americans who participate in the social safety net of entitlement programs and other benefits.
"These people are my mom and dad -- the people I grew up with, my neighbors." Biden said. "They pay more effective tax than Governor Romney pays in his federal income tax. They are elderly people who in fact are living off of Social Security. They are veterans and people fighting in Afghanistan right now who are, quote, 'not paying any tax.'"
In the biggest laugh line of the night, Ryan conceded Romney didn't express the thought exactly as he wanted at the fundraiser, then needled the gaffe-prone Biden by saying: "I think the vice president very well knows that sometimes the words don't come out of your mouth the right way."
Biden immediately responded "but I always say what I mean."
On Iran, widely backed international sanctions pushed by Obama have devastated that country's economy, Biden said. He rejected assertions that Obama failed to work closely with Israeli Prime Minister Benjamin Netanyahu and that the United States lacked commitment to a possible military strike to prevent Iran from becoming capable of developing a nuclear weapon.
"This president doesn't bluff," Biden said.
Ryan, however, insisted that Iran was closer now to having a nuclear weapon than it was four years ago, blaming the administration for allowing that to happen. He bluntly said that Tehran must not be allowed to become a nuclear power.
"This is the world's largest sponsor of terrorism," he said. "And if they get nuclear weapons, other people in the neighborhood will pursue nuclear weapons as well. We can't live with that."
Read a transcript of the debate or watch it online