My current guess for season 11 is it'll be either "Dean hunting Sam and/or trying not to" or something after Dean kills him in the last episode of season 10. I'd rather the latter, it would be at least something we don't know already. Then again, knowing the typical SPN pattern, it would be "OMG, Sam has died and went to Hell/Heaven/whatever, it'll make great season 11! *11.01 or 11.03 has come* Oh, Sam's back already..."

I'd be surprised if there was no "Cain lives!" theory. *g* I loved him, but I'm anxious about him coming back. He inevitably would end like Castiel or Crowley...