OK, as an old geezer, let me simply advise all interested readers that an inordinate (and unnecessary) amount of time is expended contemplating the latest, greatest, high-tech, guaranteed whiz-bang manstomper ammo.
I'm a hunter, and an ex-LEO. I've seen humans continue to function after more devastating injuries than any handgun round could inflict. I've seen 150 pound deer run for considerable distances after having .30-06 JSPs strike the heart/lung area.
Regardless of weather & clothing factors (from t-shirt summers to arctic winters), for either self defens or hunting, focus on two things:
1) Use a round with sufficient power to penetrate adequately; My minimum is .38 +P with 158 grain bullets. Expansion is nice, but the bullet MUST penetrate or it's useless.
2) Place the bullet(s) into the vital zone. A peripheral hit with a .50 BMG is likely to be less effective than a center hit with a service handgun.
Of course, given adequate placement and penetration, the bullet that does the most damage within the target is best. But this third factor pales in comparison to the first two, and NO bullet offers a 100% effectiveness rate.
Get a good sidearm, in a service caliber, ensure its reliability, and PRACTICE.