Ok then, so we have established that this guy is a
monster hunter, rather than a
man hunter. That means we don't have to give him a 9mm or .45, which most pros would have for humans. We get to give him something cooler.
If it has to be super-powerful and an autoloader, then you would want a Desert Eagle. The problem with that, however, is that every videogame/movie/TV show has used it before.
So, if he needs at least one autoloader, I say go with something in .45 but with super-hot handloads, or in 10mm. This could be his backup/human killer.
For his main handgun, for the 'big nasties', you should give him some kind of Revolver. Preferably in a cool chambering like .454 or .460, but the common .44 mag is also nice.
How about the Mateba? It comes in .357mag, .44mag and .454 Casull:
Someome else mentioned the .50GI cartridge, which would be cool.
http://www.guncrafterindustries.com/
Here is a 1911 style one: