Two big questions: First what kind of shooting do you do? Second, do you reload?
I don't reload (yet), but would like to. .50 BMG doesn't appeal to me that much in an AR platform, and if I did invest in one it would be its own rifle rather than an AR upper.
.204 Ruger AR uppers, however, are pretty nice. It's a great varmint round for groundhogs, prairie dogs, coyotes, etc. Shoots flatter and bucks the wind better than 5.56, and the cost and barrel life aren't too much worse than 5.56.
Pistol caliber uppers: meh... Doesn't really appeal to me, but it's not a bad idea.
Big B