I've been waiting on this Fallout for a long time and now that it's arrived I can say that it has, kind of, been worth the wait.
The main storyline, if you focus solely on it, will not last a long time. But Fallout 3 is a huge game with tons of things to see and do - it wasn't intended for you to just do the main quest and nothing else. Keeping on the subject of the main quest however the ending is terrible. You can tell the last 2 or so parts of it were rushed and the ending itself doesn't make much sense if you have Fawkes with you... which, since you get Fawkes near the end of the main storyline anyway, is just silly. This added with the fact that you cannot play the game after the main quest is complete were, in my opinion, the two major downfalls of the game. It's stupid to not be able to play after the main quest on such an open world game like this and unless you save with seperate saves you can find yourself stumped.
Bethesda have done an amazing job optimizing the Gamebyro engine (the same engine they used with Oblivion). Not only does Fallout 3 look better but it also runs better than Oblivion and load times have been significantly reduced. Though unfortunately it still seems to suffer from the odd freeze or crash here and there. The NPC's have alot more varied animations and their interactions with each other have been much improved. The animations however are still fairly bad, though Bethesda have never been good at animating to begin with. I was hoping they would at least add a forward strafing animation this time so it doesn't look like your gliding sideways in 3rd person, but no dice. Likewise aiming in 3rd person can still be a hassle (seems like the crosshair is off center too compared to where your bullets actually land) though it's much easier than it was with Oblivion.
VATS, the games answer to Fallout's AP / turn based combat, is fun to use. It's not necesarily turned based per se but you can see they tried to give it that feel (with pauses here and there between gun shots). You'd think after 100 times using it it would start to become a chore, something painful you had to watch to kill some guy, but surprisingly I still find it amusing even on my 3rd playthrough. The over dramatic deaths that sometimes occur coupled with the over-the-top gore and cinematic angles of the action keep each and every VATS use interesting.
Unlike Oblivion Fallout 3 doesn't have alot of quests, however each is a lot more fleshed out and often has multiple endings. Some of these quests can even take upwards of an hour to complete. The random 'dungeons' scattered throughout the wasteland have also had the same kind of attention as these side quests. Each dungeon area is unique and often has it's only little backstory to it, it's not just a copy paste area with some random enemies dotted around.
The dark humor and cultural references that were in the original Fallout (and slightly overused in Fallout 2) are also present in Fallout 3. Though some of the humor seems a bit forced. It was fun to run across a certain guy who is very similar to Oblivions legendary 'Adoring Fan' though :)
If your the kind of player that enjoys running around exploring the world then you will get your moneys worth, and more, with Fallout 3. However if you need direction or a 'reason' to play then I doubt you'll find this game as enjoyable. Bethesda has planned DLC on the way for Fallout 3 so new content is certainly coming, here's hoping they release a construction set so the game can really start to shine.