For defense purposes, I highly reccommend the time tested .357 Magnum.
I own a S&W Model 65 and it's loaded with 158gn .357 Magnum hollow points.
I love a handgun that shoots a flame, and this one never fails to dissapoint.
.357 Magnum is a great round and usually overlooked for the more modern, hi-cap style rounds, but I guarantee if you get hit with one, it's gonna hurt.
I like wheelguns because of the simplicity of design, with no possibility of a stovepipe, or other stoppage that goes along with the semiauto guns. You can leave a revolver for years, pick it up and it'll work.
Yea, they aren't as sexy as the other guns, but when you need a tool that works EVERYTIME, then go for the revolver.