I've used a ruger mk2 (5.5 bull barrel) for small game for years. I've carried a 44 vaquero as a sidearm for big game for five years or so. (you gotta have BIG pistol for big game in colorado). I've zapped jackrabbits and Prarie Dogs a plenty with that 22 pistol though. No mods except for custom cocobolo target grips.
But I hunt with a BUNCH of handgun hunters for big game. and they have been known to carry everything from 454 casulls, 475 linebaughs to 30-06 contender encores, not to mention wildcat XP's in calibers I've never heard of (you know SURE it started out as a 6mm/08 ackley improved until I talked to Bob over at the skunkworks.. now its a 6.5mm jdj ackerman hybrid with a... blah blah blah...) Those guys have more money than sense.. but MAN they can shoot. Ruger Blackhawk "hunter" models are very popular in my camp too. But dogging with these guys is an experience you have to SEE to believe.