I believe Set takes the cake from FO1. He's clearly hostile, but he doesn't attack you just for showing up on his doorstep. He's easy to set off, but so are many characters like Killian, so I'd consider Set a definite "neutral-passive" NPC, and his appearance, mannerisms, personal outlooks, and role make him come off as ominous, at best. He's very unsettling if you're playing the game for the first time, and even if it's your 10th time he makes your feel uncomfortable.
FO2? Well Lynette is easily the character I despised the most, yet felt forced to suck up to in spite of my reservations regarding her character. I don't know that I could define that as "off-putting" however, since she really did elicit closer to abject hatred and unfiltered disgust out of me. But then again, she's completely topped in all of those regards by President Richardson, even though he's arguably the central antagonist of the game, because he never initiates combat.
FOT had few in the way of NPCs that you could get to know very much that weren't about to shoot you, but either Barnaky or Tiduk left a strong impression of being real bigoted assholes, however I think Kerr wins here as the most unsettling character in the entire game that doesn't try to kill you. When he's first introduced, he's a bounty of trades to make that FINALLY offers something different than the quartermasters in every base, but feels almost too "nice", and every time he speaks the background noise of the medical equipment he's constantly hooked up to is somewhat unnerving. But when you find him for the last time having been torn apart and kept alive in a perpetual state of agony by life support systems, a grotesque mirror of his original state, that's just a haunting image to have to come to terms with.
As for FO3.....
In FONV, I'd say that easily goes toward Mr. House, but until you make it to the Strip and "meet" him, then Cannibal Johnson stands out the most as an unnerving character. A solitary old man lingering in a cave, denoted as "Cannibal", with the Master's Lair theme music permeating the background? That's just creepy. Nevermind that Johnson himself is a really standup kind of person, the circumstances under which you meet him are just... quite unsettling. But then you meet House. And Mortimer. And Vulpes. And Ulysses. Really, FONV is such a massive game, it's really hard to say which ONE particular non-hostile character is the most off-putting. There's just so many to choose from.
