The weapon suits the target.
Which weapons are "practical" or "best" in a given situation depends heavily on what they're used on. A shotgun full of birdshot is a perfectly practical weapon for shooting at birds, but not great for people and useless against buildings.
When firing at a single, unarmored human at short range, there's not much reason for guns to get bigger than they already are. A large-caliber handgun already can pack enough energy to incapacitate or kill pretty reliably across a broad range of impact locations. (Where you get shot is just as critical as how powerful a gun it is; smaller guns can totally kill people, even instantly, but need to be much more precise about it.)
There are three basic reasons to use a bigger projectile. One is longer range: though it may seem paradoxical at first, larger, heavier projectiles are (all else being equal) much more accurate at much longer ranges. However, handguns are not a very good form factor for long-range shooting; a proper longarm or even something like a bullpup design is more stable, easier to aim, and generally scales better at larger sizes. A handgun can only get so big before it gets unwieldy when actually used as a handgun.
The second reason is raw kinetic energy. As mentioned above, this isn't all that useful when shooting at unarmored people, but armored targets would be a very good reason to want a big ol' bullet. Even if you can't breach the armor, a larger bullet has better odds of breaking bones, knocking people down, and generally doing something useful and buying time for you to bring up the big guns. (Note that "armored targets" in this context can include animals or aliens that are naturally tough; a rhino is not going to be impressed by your run-of-the-mill handgun.)
The third reason is submunitions: something like a classic shotgun shell or a flechette cartridge. Instead of one big bullet, you take all that energy and put it into a bunch of little bullets that can each individually incapacitate or kill. This would be an advantage in close quarters (being able to aim more quickly - because you don't need to be as accurate - means you can beat an enemy to the punch if surprised), although because they're small, they tend to have a short effective range.
This suggests two basic situations where you'd want a revolver that's notable bigger than they already are: either your targets will shrug off normal pistol rounds (maybe they're wearing power armor, or are huge aliens), or you're actually using a revolver shotgun to blanket a space. In the latter case, you're arguably better served by a small-caliber, rapid-fire weapon like a submachine gun. In the former, the hand cannon is the best you're going to do for a sidearm.