Since you're using handloads I'd say that for deer sized game they're going to be about equal, with and edge going to the 45 Colt if you use hard cast bullets. But either caliber will do the job nicely.
If you're looking at larger than deer sized game the advantage for the 45 Colt grows due to the ability to use heavier bullets that should give you more penetration.
Tests done over at Sixgunner and by John Linebaugh indicate that velocity doesn't increase penetration above 1,200 fps but more bullet weight can.
So to focus your question more, what range of "four legged things" were you thinking of? Deer, hogs, moose, grizzly?