1. BIDEN UNBOUND: Look for Biden to go on the offensive in hopes of regaining ground lost by President Barack Obama's lackluster debate performance. An experienced debater, Biden is comfortable with the attack dog role. But the vice president has a history of freewheeling, foot-in-mouth moments. Will he commit another gaffe?
2. RYAN'S DEBUT: This is the Wisconsin congressman's first time on the national debate stage. As House Budget Committee chairman, he's a whiz on federal spending and tax policy. His knowledge of foreign policy and national security isn't as deep. Watch to see whether his hours of practice result in polished and punchy—not wonky—answers.
3. BATTLE OF THE AGES: It's youth vs. experience. At 42, Ryan is the same age as Biden's younger son. Ryan suggests the generational divide gives him an edge over 69-year-old Biden and wider appeal. But Biden's an energetic performer who prides himself on an ability to connect with regular folks.
4. NUMBERS GAME: Expect to hear lots about the House Republican budget plan written by Ryan. Biden's sure to criticize Ryan's spending cuts and Medicare proposal as too extreme. Even GOP presidential nominee Mitt Romney has distanced himself from some of Ryan's more controversial ideas.
5. THE MODERATOR: Jim Lehrer's laid-back approach in the first presidential debate was widely panned. This time Martha Raddatz of ABC News runs the show. Look for her to ask sharper questions and more aggressively rein in the candidates. The veteran war correspondent has joked that it might be wise to wear body armor for the job.