So my friends and I got the idea of playing boss to boss, fighting in the same environment and maintaining the environment cards in play and trash, as well as each hero's play field, deck, hand, and trash. And so we went like this.
The Team (in order) - Tachyon, Legacy, Ra, ExPat.
Where? - Insula Primalis
Villain One - Baron Blade. He did quite a bit of damage to us but we managed to get the environment to kill him for us. We were in a sorry state so we modified our house game with the 5 minute break rule, basically you regenerate one half of your lost HP when the new villain enters play (if you started the game with 30 hp and you defeated the boss with 20 hp remaining you gain 5 hit points, basically a second wind for you 4e DnD players).
Villain Two - Voss. By this time Tachyon had almost every burst card possible in her trash and we made short work of him but the environment took us down quite a bit. At this time we decided our 5 minute break rule needed to be modified or else we could keep going forever now we would use the hp total we had just after the last 5 minute break (if you had 25 hp after the last break and now you're at 15 hp you regain 5 hp)
We continued through Omnitron and then Citizen Dawn before we lost our first player. We called it quits after that, we might make the 5 minute break a flat 5 hp the next time we try it but it was a fun modification to our usual fun.