Breaking bone and/or destroying the brain or spinal cord are the 2 things that STOP animals. If the bullet does either, the stop is instant regardless of what gun or caliber it is fired from. It's obvious that a 500 is far less likely to break up or deviate then a 308 Winchester, but IF the 308 bullet could get through in a straight line and hit the vital targets it's going to drop animals as fast and a 500 or even a 600.

That's a very big "if"

That "if" is the the reason we have or use big guns with big bullets.

But adding power or bullet mass only goes so far. A poor hit that doesn't destroy the brain, spinal cord or break a big bone is not going to be any more effective at stopping a charge (or a "get-away) from a huge gun then it is from a mid size gun. I am sure the larger diameter would will bleed out faster, but enough faster to make a real difference if the animal was charging is doubtful to me. I am sure the 4 bore rifles I've made for customers would bleed out a buffalo or elephant faster then a 375, but if the buff or elephant only hammered you for 6 seconds as opposed to 12 seconds but you were dead or crippled for life in 3 seconds, I'd wonder how much you really gained with the 4 bore.

In the late 70s I had 11 months in 3 African countries and the only 2 rifle calibers I used were 308 (7.62 NATO) and a 404 Jeffery. I also got to see a few 458 Winchesters used. Comparing the 458s and the 404 what I can conclude is that all good hits were equally effective, so-so hits were semi effective and poor hits were not very effective. Old Kynoch 404 ammo shot 400 grain bullets at about 2150. New German 404 ammo shot a 400 grain bullet at about 2400. The 458s shot 500 grain bullets at 2050. I saw no difference, shot to shot, between any of them.

Bullet placement and bullet construction/design were/are vital.

All other things seem to exist for the sole purpose of giving hunters subject matter to debate, but none really seemed to truly matter in the field.