This is a good discussion & I hope more join in. There are so many variables when shooting real live game that it's hard to put a definite answer up on exactly what's going to happen once the bullet makes contact with the animal. The construction of the bullet, the velocity, the distance, the angle & of course the size of the animal & where it's hit.
None of these things things can be totally controlled in the field although we always try. Many times these discussions go straight to the top, the very biggest animals & when that happens you narrow bullet selection down to only 3-4 premium bullets, period. Of course others will work, just like a 9mm will kill a Grizzly in Alaska or a 22 LR will kill a Black Bear.
If we drop down to the main stream of big game hunting with a six gun in North America then we allow a lot of different bullets to come into play & that's where most of us hang out.
Probably 75% of the game taken by lower 48 six gunners is deer, either muleys or white tails. The other 25% would be hogs,
exotics, pronghorn, bears, elk, lions & moose. Maybe I've missed something but that pretty much covers most of it.
For these animals "most" bullets of 250 grs or above will handle anything mentioned with proper bullet placement.
I've taken all of the animals above & in 50 years I've recovered exactly ONE bullet. Speaking of my own experience I'll say if there's one place where guys can go wrong it's with velocity. That is they tend to over drive a bullet beyond it's design limits & the bullet lets go.
This is just my experience, some one else may see it different, no problem. A six gun doesn't need top end velocity to kill big game at 40-50-60 yds with good shot placement. For me that's mostly been heart/lungs but sometimes shoulders because here in the west you seldom get a flat broadside shot. It's usually uphill or downhill or at an angle, not much flat ground in the western US.
Bullet seperations, bent bullets, over expansion, bullet blow up, I've never had it, not even once & never seen it once from my hand gun friends, even on bears, elk & moose.
My only recovered bullet was this last fall on a smallish buck at 64 yds with a soft cast HP bullet, something that I seldom use. It was a 240 gr 44 & only 10 grs of Unique. I know that this bullet would have blown up if I have leaned on it hard at 44 magnum velocity but because it was much slower in my 6 1/2 Ruger OM flat top it did something totally unexpected, it stayed together for several inches. He was facing me almost straight on & I hit the big shoulder joint right on the point, this would have blown up a hot 44 HP without question. It went through the pulverized joint, one lung, the intestines & was laying up against the left hip bone & if I remember correctly weighed 85 grs. He covered maybe 15 yds, I was totally shocked the bullet penetrated that far because of the HP & the shoulder joint. The key was, I didn't over drive it. But we never know, that shot could have been 125 yds that day, I still would have taken it but a hotter load would have made more sense, or picking up the 10 1/2" 44 laying at my feet with a 4X Leupold & 21 grs of 2400 & a Keith bullet, nice to have options.

Dick