Training will overcome most of the issues. When I carried a Beretta .25 I practiced "lacing up" the bad guy target.
That meant the first shot to the thorax, the next shot about 4" higher. A shot to the throat and a shot between the chin and the eyebrows (thinner bones there). That is 4 shots, and you are just raising the sights after the first one. With practice it becomes almost automatic.
I think that four rounds placed as I described it will stop a 400 pound bad guy. You can always double up on the throat shot--but that leaves you short for the 2nd assailant.

