Basically, Doof takes away Spider-man, Thor, Hulk and Iron Man's powers, so villains like Venom, M.O.D.O.K. and Red Skull decide to join forces with Doctor Doof (Doctor Doom can cry me a river.) while Phineas and Ferb have to help out Thor, Spidey and the others.
So. Yeah. That's crazy. And awesome.