Shot placement, shot placement, shot placement. It's not a split decision between caliber and shot placement, not even close. Would you rather take a .22lr to the eye, or a 50 BMG to the big toe?
However, two shots to the same place, I'd rather have a bigger hole, and better penetration. YMMV.
"Freedom and reason make us men; take these away, what are we then?"
-Sometimes your best defense is a good reminder of your common sense-
HK USP Compact 9mm - SA XDM 4.5 .45 - Browning Medalist .22 - Ruger 10/22 - Browning Superposed O/U - Remington 1100 - Remington 720 .270