First of all, some quick obligatory notes. Debates rarely make much of a difference in election outcomes, although given that this is a pretty close election, a two-point bump in one direction or the other could be important. Debates can do other things, though, like increase people's knowledge of or interest in particular issues, or help set an agenda for the rest of the campaign cycle. Also, while it's probably not the case that JFK beat Nixon on TV but lost on radio, the medium is itself important in affecting people's perceptions of the debate.
Okay, with that out of the way, what can we expect to see Wednesday night? On that point, I'd strongly recommend reading James Fallows' analysis of Romney's and Obama's debating styles. He suggests that Romney may be the stronger debater (and has a lot more recent experience), but that he has a key weakness -- he falls apart on topics for which he's unprepared. So Obama's whole approach will be trying to find the issue or approach for which Romney isn't ready, trying to get him to make one of his "$10,000"-style gaffes.
My impression is that the debate is a higher-stakes event for Romney. He is trailing pretty significantly in the recent polls, and given how few people are still available to convert and that voting has already begun in some states, he doesn't have a lot of time to change things around. And if he's going to change things around, the first debate -- which will likely have the largest audience of any political event this fall -- is the time to do it. Obama, conversely, can win by not losing. So while both men are pretty careful and cautious debaters and not given to particularly rash outbursts, I'd guess that Romney will take a few chances on Wednesday and generally be the aggressor.
This first debate will deal exclusively with domestic politics, which largely means the economy. This is the issue that's supposed to be Obama's weak spot, although interestingly, it hasn't proven fatal to his reelection campaign -- a fact that's been somewhat disorienting for Romney. Of course, that doesn't mean Obama isn't vulnerable on the topic, and Romney will have plenty of ammunition for making a case that the economy has been underperforming on Obama's watch.
While Romney is trying to tear the president down, he will also likely be trying to rehabilitate his own image. There's some reasonable evidence accruing that Romney's "47%" comments are a big part of the reason that he's been losing ground to Obama recently. So Romney's approach in the debate will likely be in part to show that he's more compassionate toward poorer people than he sounded at that fundraiser, and in part to argue that, regardless of who's more compassionate, his plan will do more to help them.
Again, these two are pretty skilled and cautious people. I'm not expecting any sort of "You're no Jack Kennedy" moment from them. But given how much ground Romney still has to make up, I'd expect him to throw the most punches.
I make some of these points in an interview I did recently with Lance Gould of the Huffington Post. You can see this below.