[scrubcedar]

Your .357 with shotshells sounds like a good bet. If it fits your hand well it's perfect.
If this is a question that has to do with justification for a new pistol that's different.
My single six has dispatched it's share of prairie rattlers with head shots from closer than I like to think about, so I know it works in my neck of the woods, but you live in a completely different type of place if you have cottonmouths.
Does a single six work on snakes? You bet. Done it.
The reason it worked so well was because the gun at that point was almost a natural part of my hand. It's still my favorite gun because it points so incredibly well.
Find a gun that the holes in the target seem to naturally appear where you want them and caliber isn't nearly as big a deal.
I've been where you're at in terms of snake strikes. When split seconds matter I want what I know I can hit the snake with, and that means what points the most naturally for me.