The archangel Michael takes John Winchester as a temporary vessel. He explains to Dean that he has many potential vessels that are suitable to hold him because of their bloodline, which stretches all the way back to Cain and Abel.
Castiel, speaking of his early life, mentions his memory of Cain and Abel.
Cain reveals that Lucifer tried to corrupt Abel to turn him into his "pet." In order to stop this, Cain made a deal so that Abel's soul would go to Heaven and in exchange Cain's would go to Hell. Lucifer agreed on the condition that Cain kill Abel. Cain did with the First Blade and became a demon and the first Knight of Hell.
When Cain and Dean fight, Cain tells Dean that their stories are the reverse of each other: Cain's started when he killed his brother while Dean's will end when he kills his. Cain tries to kill Dean but is killed by him instead.