A couple quick hitter ideas I have in mind include:
Rowena using a spell on Dean to seduce him in to doing her dirty work for her and obviously fucking around because who could resist?
Demon's blood turns Sam stronger. What happens if Dean unknowingly is fed/given Succubus blood? It leads to him having a far easier time seducing women and he even ends up bedding some that he never planned or thought possible. (Death/reapers, vampires, demons, etc). Can be a series of one offs or something more long-standing!
The hell is a demogorgon? Nancy Wheeler, explain. (Or someone else from the series Stranger Things).
Open to other pairings, ideas and the like. Feel free to toss something at me and we can try and make it stick!