I spent quite a bit of time looking at both the 500 and the 460 and finally choose the 460 with 8-3/8" barrel. I picked that caliber over the 500 for several reasons:
-- It accepts multiple caliber rounds and thus allows for relatively cheap practice, plinking, etc. The 45C is a fantastic round (perhaps my favorite) and abundantly available at reasonable prices, and the 454 Casull is an excellent high-power round and great hunter on it's own right.
-- The ballistics of the 460 are slightly better than the 500 in terms of trajectory (flatter), while the 460's energies are notably higher. The 460 puts a 360 gr (Bufallo Bore) bullet out at 1,900 fps while the 500 puts out a 400 gr bullet at 1,675. In terms of ME that's 2,860 versus 2,491 ft-lbs.
-- The 500 does have a slightly higher TKO (45 v. 50 at the muzzle for Buffalo Bore) but the difference is pretty minor and I think more than made up by the flatter trajectory and thus better bullet placement for any long-distance shot (and for anything close both rounds are more that sufficient for anything you're likely to shoot). And the 500 can deliver a 440 grain bullet while (as far as I can find) the largest factory ammo available for the 460 is 360 grain. Though I suspect that gap will close with time.

The one significant advantage of the 500, IMHO, is that a wider range of barrel lengths are available for new production. But there's a pretty good selection of barrels in used 460s. That said, I very much like the 500 in a shorter barrel just for the cool factor!