True. I recently picked up my never-finished Fallout: New Vegas playthrough. I play a reasonably good guy like I usually do in RPGs. Stellar karma, usually trying to resolve quests in the best possible way, even trying to get out of situations without killing anyone if they don't try to kill me first. I have no qualms about shooting raider-type people but they have no qualms about a lot of really nasty things and it's a tough world. Still, I try to be nice to civilized people.
Except for Caesar's Legion. While originally I intended to be neutral for as long as possible, a Legion patrol decided to attack a trader I was going to do business with. Not wanting to lug my full inventory to the next town (and not appreciating being caught in the crossfire) I defended the trader against what I perceived to be random attackers. My faction karma immediately fell to "vilified" and the Legion now sends hitmen after me every couple ingame days.
Now, despite being a good guy, I've heard "The Caesar hat marked you for death!" one time too often. Originally I'd shoot the Legion assassins out of self-defense. By now I take perverse joy in confusing their AI (to the point where they follow me around but never attack or speak to me), leading them into minefields, pitting them against deathclaws or just taking off their limbs using high-powered sniper rifles before they're anywhere near their guns' effective range. If the Legion wants to see me as a horrible murderous sonuvabitch, I'll be happy to indulge them. (Of course it helps that the Legionnaires go out of their way to be pricks anyway but "The Caesar has marked you for death!" has done more to sway my opinion towards inflicting grisly violence upon them then their other actions ever could.)
I still try to be exceptionally nice to other people. Sometimes I even look up the endings of quests when I'm not sure if picking a dialog option is inadvertantly going to ruin someone's life. Making the simulated wasteland a better place is a big part of what I enjoy about the game. But yeah, if the people I meet work for the guy who feels so insecure about his army that one random firefight is enough for him to commit squad after squad of assassins to getting on my nerves when I least need it I'm going to paint the desert with their liquefied remains and I'm not going to feel bad about it.
So yeah, someone who usually tries to act nice can make big exceptions if they're just pestered often enough. (Of course it helps that in this case the pestering usually involves a lot of gunfire.)