I've owned a 6.5" 500 and loved it. I only sold it when I needed money for a wedding (I don't regret it). With that said however, I am back in the market for just the right 500. Here are the reasons why the 500 for me, and then I'll share some ideas of where the 460 would win out.
For me, I want maximum effect on a big hairy things that want to kill me. If I am in a hunting situation at anything longer than 20 yards, I will use my 375 Ruger which I will have with me. I reload, so I can make loads easier to shoot and right up to my personal limit. And with the x-frame, that personal limit for recoil will be much more powerful than with any other platform (points for the 460 as well!). I prefer handier guns with barrels only long enough to have a decent sight radius and get most of the cartridge's potential velocity and limit the amount of powder burning after the muzzle, and the bigger bore of the 500 allows that. Both the 500 and 460 have a ton of powder to burn, about twice as much as a 454 casull!
Now, in a lot of ways the 460 is similar to the 500 when viewed from a wide perspective. Both make other big bores look like 357's and 38's. But they have entirely different advantages over each other. The 460 has much better versatility for the NON-reloader with factory 45 colt and 454 casull ammo. If one is intent on never reloading but will shoot it more than a hundred times, go no further than the 460 unless they buy a new car every year. The major advantage of the 460 is it's speed. It's all about adding speed to the same 452" bullets of the 45's and 454's. This is the cat's meow if one is looking to take 100+ yard shots or set up with a scope. It needs a long barrel to have a significant advantage over the 454.
In summary, the 500 is a defense weapon, the 460 is a hunting weapon.