Aliasalpha: It depends drastically on what the difficulty levels do, if its just buff/debuff for hit points or weapon damage or something then you really don't learn any less by having it on moron, easy, medium, hard, insane or omgwtfbbq because the mechanics are the same.
A friend and I were talking about an ideal difficulty option the other day, instead of making things easier or harder with hitpoints, a game could give you more to do. We were thinking that in splinter cell on easy you have to hack a computer to get data but on medium or above you trigger an intrusion alert and have to quickly run over to the comms room with the firewall (picking or smashing the lock) to disengage it before it can broadcast the alert
I know at least some of the Metal Gear Solid games change the enemy layouts on different difficulties, granted it isn't really multi-player.
GoldenEye was fun for adding objectives too.