So far, not really. There are weekly campaign challenges available that require you to play with one or more skulls on. Personally I skip these, as these multi-skull challenges border on sadistic. With the added difficulty, the missions usually take forever, and the payout XP-wise isn't that good. Generally speaking you can spend the same amount of time playing any Multiplayer game type and net more XP... with a lot less frustration. I guess there's bragging rights, too.
If you complete the game with all the skulls on AND the while on Legendary then you unlock 50,000 XP from Waypoint and this emblem http://i.imgur.com/dYUwU.png :)
Very good info. I didn't know that at all. I dunno when I'd feel up to embark on this challenge. It sounds brutal. I had a lot of difficulty with some of the older challenges that required you play with just two skulls on. I don't know if the drywall in my game room could take it if I tried to beat the game with all of the skulls on.