A friend suggested that Fallout 3 is "too soulless for its own good". I have to agree. It's a great game, certainly. But the relentless dreariness works against it.
Dynamics in mood and tone are vital for any RPG, and games in general. This is particularly true for visual presentation.
Fallout 3's environmental design is really impressive, particularly due to the scope and level of detail. But it's bleak, almost without exception. That certainly fits the story and the overall tone of the game. However, too much consecutive bleakness ultimately has the same effect it would have in true life -- it drains enthusiasm and motivation.
With a game so big, there are undoubtedly factors at play which differ from player to player. If you initially focus on wandering and sidequests, as I did, then it can be a very long time before you enter Tenpenny Tower or the wooded sanctuary. For perspective, I've spent dozens of hours in the game and explored much of the world, but am hardly beyond Tenpenny in the main questline.
In any case, it's good in any RPG to offer a variety of environments with different color palettes and tones, as well as missions/quests and encounters with a variety of moods. Dynamics provide freshness, which is necessary to maintain momentum and excitement. This is one of the reasons I think color palettes and elegant designs like World of Warcraft uses are the best visual design option for the majority of games.
I still enjoy Fallout 3 (though I haven't played in a while), but the different areas and experiences of the gameworld started to blend together after a while.