I think part of the Fallout defensiveness was that the Fallout fanbase was burned heavily by Interplay's last foray into the franchise, Fallout: Brotherhood of Steel. F:BoS was somewhat like that mentally retarded cousin you try never to think about, but unlike the latter, which you can utilize in moments to sound like you give a care about those less fortunate, F:BoS just remains a crappy game. What most of the defenders worry about is that Fallout 3 is going to end up like Fallout: Brotherhood of Steel, the FPS.
I don't mind the move to 1st/3rd person myself. It was overall inevitable, and it'll be nice to see artists really make detailed rooms and show with great detail what this post apocalyptic world will look like. Hopefully they make it feel more like Morrowind, where everything is hand placed and has a purpose, rather than Oblivion. Walking up to get a good, close look at the scuff marks on the Vault door, seeing how paint has been removed from old vehicles and houses, et cetera, will be really nice.
What I personally hope isn't lost is the real feeling of choice and freedom found in the first two games. Being able to solve quests in multiple forms, being able to move from town to town, then go back to old towns to continue their quest trees (though, kinda frightening that 3 months later, that same widow is sitting in the same room waiting for that same lost boy in the same well...) Bethesda hasn't really shown that it's going to make an attempt to get that same feel in the game. Sure, at the beginning they promised that sort of thing, but looking at all the new videos, I'm sure that was forgotten with giant mantises.
While getting rid of the pop culture references isn't completely detrimental to the plotline, pop culture really does play a large, underlying role in the game. It's about a future that was probably destroyed by its own consumerism (see also: System Shock). The whole game, in itself is pretty much a reference to "Mad Max" as a whole and some refer to the game as "Mad Max RPG."
Changing the combat/feel of Fallout isn't going to really hamper what the fanbase is looking for. Fallout Tactics was a brilliant game that turned the RPG into a SPRG with both real time and turnbased options (much like X-COM: Apocalypse), and yet the game felt very "Fallout"y. It's about choice and consequence, it's about sometimes being a baby-eater to be Mother Theresa (to use the allegory by Yahtzee, which a friend of mine, prior to the Bioshock review used to call the "Ghandi or Dick" morality choice), it's about feeling like after every little quest and mission, feeling like you've actually made a change in each town, that you can effect the world through your actions. If Bethesda can do that using a FPRPG, more power to them, but mini-nuke launchers aren't the core of Fallout, sure, they're going to be very fun, but the real testament will be, will your other option be subterfuge or diplomacy? Or will it be a Gauss Rifle? The latter, of course, falls into the problem The Elder Scrolls keeps having.
Granted, before any notes any sort of "hypocrisy" that I really, really like Suikoden II (A very linear RPG) and yet, touting on and on about freedom. There is a place for linear RPGs. If the story and characters work, then a linear RPG is going to work, in that case it's about playing a story, not so much about playing a Role in a game. Fallout was about being in a Role in the world.