It's almost like "railroading," when you play D&D or something and the dungeon master comes up with all these convenient events to force the players to continue a quest if they screwed it up.
Yeah, that's the age-old roleplaying problem - how do you get your players to go into the haunted house when they decide to walk right past it?

It's a less obvious problem in a videogame (because if you want to keep playing long enough, you're going to go there eventually...) But I still think it's probably a concern. Just like a good GM will get their players into that house without making it feel forced, the ideal game designer should be able to get you through the Main Quest, at least, regardless of who dies maybe? (I had this one GM who was so good at "winging it," that he'd come up with a completely new adventure on the fly if we decided to bypass the pre-planned story entrances - and then do it in such a way that we still ended up where he wanted us to be in time for the next session, without us really realizing it. That's obviously impossible in a videogame, but you could probably get some of that feeling with alternate routes to a Quest, etc.)
Another thought, though - for the most part I'm not a big fan of NPCs dying due to random events. Like the time I travelled past Arefu mid-way through the game and by the time I even realized they were under attack by a group of radscorpions, they'd already slaughtered half the town. If I murder someone, that's one thing. Or if they die while I'm escorting them somewhere, etc. But in that Arefu example, I was just walking by that place - I wasn't even intending to go up there; but simply happened to be passing through that cell. If I hadn't heard some gunshots in the distance I wouldn't have even known it was going on in the first place - they would have all died and I'd never have been any the wiser until Lucy West started talking bad about me even though I'd finished that quest the "good" way. For something like that - if there's even a possibility that they're going to die, then that eventuality needs to be accomodated. (I consider everyone treating me like I'm evil whenever the Arefu quest comes up in conversation or over Three Dog's radio, even though I did the exact opposite, to be a bug...)
On the other hand, if I go around slaughtering quest-givers - there probably should be some consequence to that. If I end up killing someone that was tied to the Main Quest - well, too bad. That was the player's decision, then. If I make a mistake in combat and end up dying - I have to reload. If I make a horrible mistake like killing someone that I'd need for the MQ, then I figure that's the sme. I might be biased, though - I grew up playing games where it was possible to completely mess things up like that. Like those old Adventure games where if you forgot to pick up that one important object at the beginning of the game that you need to complete a puzzle later on, you were just going to have to reload. (That's an outmoded game design, but I think if you're killing NPCs, I wouldn't have a problem with that being a consequence...)