Spider-Man 2: 300 enemies.
This is assuming you're playing the game the way our focus testers did, by going straight for whatever bright and shiny dot is on your HUD rather than doing any of the side missions or trick challenges.
Only a quarter of that number is in story missions, so it's technically possible to win the game after beating only 80 or so enemies.
I determined this number empirically, by playing the game at work the last couple of days when I should have been working. The way Mark put it: "Jamie's like an expensive, inefficient tester."
Somebody asked me who Mark Nau is, btw: he's one of the brainiest guys at Treyarch. We're sharing the Creative Director position on our yet-to-be-announced project; he's the brains, and I'm the...I don't know what...the guy who likes Spider-Man and third person action-adventures a lot. We share an office, so I frequently hear his opinions, and can share them with you. His CV: http://www.mobygames.com/developer/sheet/view/developerId,26235/. He also writes a Secret Blog that's not about games that I don't actually know the link to but the intrepid reader may be able to find it for themselves.
Both the Prince of Persia numbers and this are kind of eye-opening for me: if you'd asked me, "How many enemies do you think you fought in those games?" I would have told you around a hundred or two. The reality is two or three times that, so in this one sense the project has already been worthwhile, giving me a more accurate idea of just how much fighting is really in these games.