Cain will always loom over Dean with his prophecy that Dean would one day cross the line and will do the one kill that will break him forever (Castiel).
The threat extends beyond what Cain can even guess, because from the moment Cas entered the narrative, his purpose has been to shield Dean. He is (many times) the only one that stands between Dean and a certain death.
The problem is that the more Cas sacrifices, the less Dean wants him to. That's for me what the whole Cain-Colette parallel means: the more that person loves you, the more you share your burden with them and the more that burden will kill them.
I wonder if Dean hears the ghost of Cain laughing after Castiel dies again. I wonder how many times Dean thought that he would forever be unclean / marked / cursed by it. If he sat on the floor and thought loving me is what killed him as the many times Cas did something to protect him came to his mind.
