It has been my experience that when this debate comes up, the guys advocating the bigger is better, or this and that special sauce seem to overlook the most important part, which is training. Of course they can argue the absurd and start making comments like," well, then the .22 should be the tits if shot placement is everything". Penetration is necessary for the round to work and if a .22 will do it in all of the scenarios you expect to encounter, then more power to you. Further, by accuracy I mean the shooters ability to put hits where they want when they want.
I wont say one way or the other except to relate this fact. I had a great uncle who was a deputy sheriff in Washita county killed in the line of duty by a single .22 shot to the chest. So take that for what it is worth.
Caliber selection for a round you intend to depend on to save your life should be determined by reliability first, accuracy/penetration second, and special sauce a distant last. As long as you satisfy those requirements for the anticipated threat then have at it.
Am sorry about your uncle, I hope help got to him and he did not die alone on the road. I hope they got the guy that shot him, too. And I hope he got fried for doing that.