If my .22LR was more reliable (it's pretty good, but not as good as my .40S&W) I'd gladly carry that. You can say all you want about ballistics testing, gelatin, FBI this and that, but the .22LR has been used as an assassin's caliber for a long time. It ricochets off bones, causing more damage. If you disagree to it's lethality, I'll gladly let you stand downrange while I fire.
A .380, or almost any round will do the job with proper placement. I carry the .40S&W because I used it for years as an officer, I know it works when I need it to, and I trust it with my life. It's saved my ass before, I'm sure it can save my ass again no problem.
A .380 to the heart is more effective than a .45ACP that missed. Whatever you chose, become proficient to the point where you can not only operate it with your eyes close, but can do the same one handed, weak handed, in awkward positions, etc. A situation is not going to allow you to think "okay, left foot back, right foot foward, extend left elbow.." and get into a "proper" Weaver stance. You may be on the ground, you may be in your vehicle, you may be seated; know how your firearm reacts and have a plan for almost every situation you can imagine. When you get there, learn and train more.