Dogmeat, in Fallout. I did everything I could to keep him alive the entire game and succeeded, somehow. Easy up till the final base. Then it's not.
I also use a mod in Morrowind that lets me turn freed slaves into party members. So I'd go around freeing slaves and raising an army. Good times.
Anyway what's the difference with this topic from an other storyline topic? Because there are some moments from Albion and Legend of Mana that come to mind but they're pretty storyline-based NPC stuff. Anyway.
Albion - You get sent on a sidequest to essential get some magical boner pills for the king of some village. I'm not making this up. And in the process you discover this mute christ figure Crazy oversexed German game designers.
Legend of Mana -
<Matilda> Even though we're dead, I forgive you for everything you've done and still lov-- <Irwin> Go fuck yourself >:|
. Also anything involving Pokhiel or Putty because they were creepy as hell. Same for the Dudbears. I mean most of the NPCs were vaguely unnerving but those guys were just like "STOP LOOKING AT ME. EVIL."