there are 5 waves in a round, 3 rounds in a set, unlimated sets in a game. New skulls turn on/off at the begining of each round. From all the footage at E3, and all the videos, it seams that "Tough Luck" is the only skull that turns on at the begining, no other skull can. However, Bungie made a different game for E3 than what they accualy used in the game, so they might have done this just for giggles.
At a certian point (unknown how far into the game) all skulls will be active for the remainder of the game.
[Edited on 08.17.2009 11:57 AM PDT]