(Obligatory spoiler warning in advance)
I'm currently playing through Fallout 3, having played through Fallout 1, 2 and Tactics countless times. I've finished the main storyline, and I'm working my way through the DLCs at the moment.
Let me begin by stating that I think it's a good game. It's fun, it's interesting, the gameplay's all very fluid and whatnot, but I'm not quite sure I like what they've done with the series. Paraphrasing what people have said earlier in the topic, it's a good game - but it's not a good Fallout game. I can certainly agree with that.
It all started off nicely - character creation was cleverly made, all of the growing-up stuff seemed pretty well thought out. But upon the escape from the Vault, everything became a bit troubling. I mean, you've lived in the Vault for all of roughly nineteen years. You've spent all of that time in an incredibly isolated community. The small number of people in Vault 101 would've all known each other immensely well. I'm not saying that they would've had to have liked each other, but when someone's been with the same group of people for nineteen years, I'd expect community cohesion to work out pretty well.
Now, of course, the Overseer wields most of the power in the Vault, and I understand that there's a lot of propaganda which reaffirms this in the minds of those living there, but I still can't get my head around the way in which the guards suddenly turn into mindless, cold-blooded killers when you're attempting to escape. Would they really shoot people they've known for at least nineteen years because the Overseer told them to? I suppose I just thought it was unrealistic. Maybe I've misinterpreted it, but I'd have thought that the Overseer wouldn't have disclosed the Vault Experiment (in this case, 101 being permanently shut) to his mooks. And if he had, why would they have been willing to callously murder people for the sake of it?
I don't have time to go into more detail at the moment, but there were quite a few other things in the game that I thought didn't make much sense when I was playing, so I might jot them down later. (Presence of super mutants, FEV as a convenient plot device, return of the Enclave, a very black-and-white moral choice system, etc.)