Most of these answers seem to be based on fanfare, and I agree... however if you're asking about the biggest fight. I think there are two, and they both only happen in the event of two specific victories.
When/if Overeem beats Bigfoot, he won't be fighting JDS in my opinion, they'll shoot him straigh at Cain, as they should. That will then be the biggest fight.
Now, as a die hard fan like all of you. It's amazing to me how many people still haven't witnessed Pettis's wall kick to Henderson from the awesome WEC days. Point being, the UFC marketing machine is awesome and powerful enough to push the living crap out of Pettis/Henderson II, espeically with Henderson no doubt gaining a lot of fame with his performance on FOX. Of course that can only happen if Pettis gets the best of Cerrone.
Those are the two fights I could see doing big Pay Per View numbers over the next six months.