Now, I DO appreciate the fact that a large-caliber projectile imparts more energy than a small one, but I think it’s effectiveness is overstated. (Note that I said “overstated,” not “inconsequential.”) Deep penetration and big shock waves are all fine and dandy and make very cool slow-motion videos of twelve-inch blocks of ballistics gel with t-shirts draped in front – but heart and lungs are less than THREE INCHES from the surface. Not much penetration is required for a lethal wound.
So, whether one’s other considerations are budget, weapon size and/or weight, feel (grip shape, balance, recoil…), or looks, the gun one chooses should be one that will RELIABLY dispense bullets with every squeeze of the trigger and be one with which the user is PROFICIENT. (I’m guessing many people buy guns and don’t practice much with them.) If ammo cost is prohibitive, then by all means get a .22 and get good with it. The ammo is plentiful again and prices are generally under 10 cents per round. No matter how big a punch is packed into the round you choose, if you can’t quickly draw, aim, and shoot accurately with it, you will likely inflict just a flesh wound or have an outright miss. Then, what? If your life is in danger, you need to disable your attacker. If you can become proficient with a large-caliber weapon, great! Oh, and, by the way, if reliability is as important to you as it should be, take a close look at revolvers. They have none of the negative feed and eject issues of the semi-automatic pistols. (I’m particularly fond of magnum revolvers, .357 and .44.) Everything taken into consideration, I might prefer a large-caliber weapon with which I am familiar. However, even in a tight spot, I’d have no qualms whatsoever about using a .22 with which I’m familiar.