This is not an unusual question and one that I receive regularly via Email and frequently see posted on various firearm forums. Usually the handgun make/type, caliber as well as premier load within same are not included in the same post or question. I lumped them all together because for my answer, it makes no difference.
It is my opinion that any caliber ballistically able to produce both expansion and approximately 12” penetration in 10% ballistic gelatin is potentially a capable performer against human adversaries; many shooters will insist on absolutely nothing less than 12” penetration. Yet others prefer no less than 14 to 16”.
Some calibers meeting these requirements are more “powerful” than others but at a cost, usually increased felt-recoil which translates tougher to control for accurate repeat shots. If you can manage the more potent, harder kicking caliber or load, use it, but by “control” I suggest that this includes not only the usual two-hand hold, but single-hand shooting (right and left) as well. At 5 yards, one respected law-enforcement trainer suggests that with a 2-hand hold and starting from a low ready position, we be able to get no less than 5 shots (no misses allowed) into a target measuring 8 ½” tall x 5 ½” wide, i.e.: the size of a folded piece of typing or notebook paper in 2 seconds or less. It would be nice to be able to do that with either hand as well; perhaps something on the order of 5 shots on the same size target in 4 seconds would be a starting point for practicing one-hand control?
Some already see that this is leading up to the old saying, “Use the most powerful handgun you can control.” It is, but I believe that too many of us read or hear this but what registers is, “Use the most powerful handgun I can buy.”
Throughout this site I have listed information on my own preferred loads in various calibers for folks who might be interested in such information.
I cannot advise you on the “best” handgun type for you but have tried to provide information that might be of use to you in doing so. If interested, it is here:
http://www.hipowersandhandguns.com/choosing_a_defensive_pistol-Individual%20requirements.htm
It remains my belief that the “best” defensive handgun is at least 9mm or .38 Special and one that the user can control for quick and accurate hits at ranges from about arm’s length to a few yards. The willingness of the shooter to use deadly force if no other reasonable alternative exists coupled with the competence to do quickly and accurately do so means more than “best” loads, calibers or handguns.
See you at the range.
Best.