Does Trump hit Cruz, and if so, can he do it effectively? The moderators will almost certainly prod Trump, but he might not take the bait. Even if he does, Cruz will do all he can to duck, cover, and deflect, assuming Trump, the moderators, and the other candidates let him get away with it.
Is there a Cruz versus Rubio clash? Again, not sure either of them will seek it out, but the moderators would be foolish not to try to stoke one, and if it happens, it will be fascinating: arguably, the two most fluid communicators on the stage going after each other for the first time.
How does Rubio fare defending or explaining his work on the Gang of Eight bill? It hasn’t come up in prior debates, but is hard to believe it won’t tonight. Rubio is quite sure-footed talking about it in interviews, but a debate is different. By the way, almost everyone on the stage has some reason to go after of Rubio — either for political reasons (he poaches part of their vote–e.g., Cruz, Christie, Bush, et al.) or because they strongly disagree with him on substance (Trump, Paul).
And some others: Does Christie continue to stand out with his forceful performances? Does Bush keep himself in the game by exceeding what are now quite low expectations these debates? Is Carson simply an after-thought? Can Kasich be even more annoying than last time?