The first time was with their father. He’d been the unquestioning obedient son for 26 years and then he had one year with Sam and suddenly he’s talking back to his father and questioning his decisions.
The next time was with Lisa and Ben; he chose SOULLESS Sam over the woman he loved and the child he wanted. Considering how much Dean had wanted a family his whole life…man.
Then there was Benny, loyal loving Benny who fought by his side in purgatory and was the most bestest friend a body could ever ask for. He got left by the wayside because Sammy no likey. Bad Sammy.
Crowley…Dean’s mistress, his bestie, his sidekick, his bromance…The one who was there when Sam threw him out – okay to be fair Sam didn’t ‘throw’ him out; he chose to leave because Sam was mad at him. But then when Sam came back and said ‘look dude I’m back. ditch the baggage’; Crowley was ‘winchestered’ immediately.
And then there was Demon!Dean. Who told Sam…Let Me Go.