I think it is wise to have a topic like this, because the people at Beth or Obsidian might see it and consider doing the things we suggest. At the very least NV seemed to have explained a little about the new plasma rifles and whatnot. The Institute might be a rather convenient way of filling in the plotholes of FO3 and explaining away its inconsistencies, though some people might think that having the Institute as another great conspiracy faction would be rather cheap and unoriginal (actually I'm one of those people).
Here's a list of the most popular things that people question whether they truly have a place in Fallout.
Mothership Zeta: The most obvious one probably, lol. If it had been less cliché and had not implied things that destroy the point of the series there wouldn't be near as many problems with it, but as it stands... IMO it should be declared non-canon or at least severely tweaked. The "jet trip" suggestion is my favorite.
Vault 87: Presents too many inconsistencies. The idea of it is not that bad, even if it was just a way to show new players "FEV's [censored] up yo", but it has to be tweaked so that it will fit.
Little Lamplight: Fallout 3's settlements aren't that high up in the makes-sense department, but at the very least they can be explained in you head. This one just can't be explained. It's fairy tale bs. This should just simply be non-canon.
Vault Zero robots: Okay, this is really just my opinion, but the Vault Zero robots have to be explained. It just makes no sense to me that those technological advencements just were there simply and nobody gave a [censored] about it. It's like having today's computers but the corporations and the average person still uses outdated stuff.
Androids: To some The Replicated Man quest suggested that the androids are insanely human, which is unrealistic even by Fallout Science standards.
Too many DC buildings intact: Okay, I'm not sure if this is an inconsistency... Did the Game Guide say that DC had it bad? If not, then we can't know for sure if the damage in DC and the surrounding area was done by ICBMs. For all we know someone could have pulled a House on DC and probably some of the other major cities and the majority of the damage was done by something else.
Old World Blues: I myself think it fits into Fallout perfectly, but some do not think so and think it should not be a part of canon.
Oasis: Harold traveling that far makes no sense. I can accept large armies travelling, especially if they have vertibirds, but a single mutant for no reason? Hell no.
Did I miss any other major ones? Naturally I did not include stuff that has already been declared non-canon (all of PoS) or questionable things that already became a part of the franchise whether we like it or not (tribals and the stupid evil Vault Experiments).
Anyhow, the thread is for what you think should be tweaked and suggesting exactly how they should be tweaked. Of course some of these can be just simply not mentioned at all in any of the future Fallout games, so how they fit into Fallout will entirely be up to your head canon.