Certainly, the next time somebody says "see, they're all the same and you should vote for a third party" (the argument often used to favor Nader in the Bush v. Gore race of 2008), you'll be able to argue persuasively that, in fact, "they're not all the same". In the American political system, only the Democrats and Republicans matter. That's just how it is.

Obama is certainly in trouble, at least versus a "generic Republican" candidate. He's taken a shellacking from the right ("Communist!") and the left ("he abandoned progressivism!"). There will be less enthusiasm for him than four years ago. There will (likely) still be high unemployment. Obama's not going to get any love from the Republican congress for any sort of jobs program since it's going to require stimulative spending. All of those indicators say that Obama is going to have a hard time.

Conversely, once you switch from "generic Republican" to any of the people actually likely to run, Obama probably still has a chance. Maybe Huntsman could have crossover appeal, but the others are all competing to see who can be as right wing as possible. Really, it's a race between depressed left-wing turnout and increased right-wing partisanship, making the "middle" into target that's moving rightward. The open question is exactly where this middle ground exactly is. It will determine whether Obama wins in 2012.