I chased heavy revolver loads for a long time, looking for maximum velocity. Since then I've seen the results of animals hit with big slugs at 1200-1300 fps, and I just don't see the point of loading revolvers beyond those velocity levels, regardless of their design strength.
Today, unless I specifically wanted expanding bullets for an application, I'd be content with something that drives the hard cast slugs 1200-1300 fps, for any large North American game. These are non-expanding bullets, whether you drive them 1200 or 1500 fps, and adding more fuel doesn't accomplish much. The nose profile certainly can affect tissue damage but that's independent of the powder charge. That level of loading is fine in a strong .45 Ruger or Freedom Arms, or a .44mag S&W. It's not appropriate for a .45 S&W, or a Vaquero, let alone a Colt SAA clone.
