The only forte the 500 S&W has is it's available in a big handgun
Heck, Quick, I think you are being overgenerous at that! :grin:
When all things are considered, eg., case capacity bullet weight, BC, sectional density, conventional handguns begin to lose effectiveness when calibers exceed .45. .475 at the most, IMO.
Seyfried did a lot of killing with handguns in Africa in .45, .475 and .50 caliber. In the end he pretty much wrote the .50 off given the poor sectional density and penetration of the .50 bullets in typical wheelgun bullet lengths.
IMO, there is no diff in the long gun dept. .50 caliber and .45 caliber bullets in similar weights seem to favor the .45 for retained energy, velocity and terminal penetration. Only way to match a 500 grain .45 cal rifle bullet at 1400 fps with a .50 cal gun at the same velocity is to shoot a 650 or heavier bullet out of the .50 at considerable increase in recoil but not that much return in terminal performance.
Just my not so humble opinion