Sam and Ruby

Sam and Ruby have a strange relationship. At first the two were sort of allies againist Lilith. Although Sam never really fully trusted her at first.

Sam later starts trusting Ruby near the end of Season 3. Then in Season 4, they become lovers. Ruby in a why is also Sam's drug dealer as well, since she gets him hooked on Demon blood. But when her betrayal to brought to light, Sam helps Dean kill her.

Background
Ruby did know about Sam before they met. She knew he was the last surviving special child that Azazel had plans for. Before they meet face to face, Ruby watched Sam from afar. Sam did notice Ruby following him though. But when he turned around she would vanish. They finally do meet when Sam is overwhelmed by three demons at once, and she steps in.