The debate, moderated by ABC News' chief foreign affairs correspondent Martha Raddatz, was wide ranging, touching on foreign policy, taxes and jobs and abortion.
In a heated exchange over taxes and the health care act, Ryan said the middle class would ultimately end up paying for the administration's entitlements.
"Watch out, middle class. The tax bill is coming to you," Ryan said.
Biden was emphatic about a U.S. withdrawal from Afghanistan by 2014, insisting that it was "the responsibility of the Afghans" to secure their own country. But Ryan attacked that point, saying it was irresponsible and dangerous for the Obama administration to announce a deadline for withdrawal.
Biden said Obama had pushed for the toughest sanctions against Iran that the world has ever seen and he was "quite confident" that the U.S. could strike Iran if necessary.
Ryan, however, said the administration had not taken a hard enough line with Iran and was "projecting weakness abroad."