Since I don't believe there's very much flexibility in terms of storytelling when it comes to the Predators, my ideas below range between not completely serious and not at all serious (mostly the latter). I don't mean for them to be taken as being all featured in the same film and my apologies if any of this appears in the EU.
-A Predator and a human hunter of comparable skill and ferocity are hunting each other. Somehow neither of them realize they are the prey.
-A group of Predators on a training hunt (no aliens!) discover that if one removes their technological and physiological advantage (or otherwise removes the power gap), their human prey outclass them in every way. TV Tropes would categorize this as "Humans are warriors", yes?
-It is revealed that humans are not hunted for sport. We're hunted because we seriously creep them out. They can only stand to look at us when we're skinned. It's the flabby mouth covering and wispy hair that does it.
-A Predator is on the hunt for particularly challenging quarry, Captain Tuttle, all evidence of whom is planted by trolling clan-mates.
-"Don't cross the plasma bolts."
-The year is 22xx and humans have nearly been hunted nearly to extinction. Conservation efforts go horribly right and we eat their crops.
-The first two films retold with everything run through a Predator-vision filter shaky-cammed to hell and back. The result: the Predator's version of found-footage horror. "An experienced hunter. The end of the universe. He thought it was going to be an easy hunt. He was wrong."