On the premis that we are talking about handguns only:
For two legged critters .50GI
For 4 legged .44 Magnum.
That said, these are the largest that I would carry, not that I do.
Currently I carry a .357 most of the time, for either. I do sometimes carry a .45 (ACP or Colt). Hopefully in the next few months, I will add a .44 Special to the carry routine.