I'll address a few points.
3. Changing ED-E to make him a Navarro creation seems a little convoluted and wouldn't explain all the shit he's got on him, which was really the best thing about him (he doesn't talk, he's all visuals). Since the Capital Wasteland is being disregarded, we can safely consider it unestablished virgin territory and use it to our advantage. I think the best course of action is to tweak the dialogue in ED-E's tapes to never mention the Enclave by name but to subtly imply he's from a remnant group of theirs, maintaining his mission and foreshadowing the remnants in the Mojave.
Alternatively, the Enclave thing could be scrapped entirely and he could be a tool used by Ulysses; instead of the weirdly shoehorned thing about the Divide copying him, Ulysses could have simply reactivated the facility and had it produce eyebots to send away into the wasteland for whatever reason (maybe to observe, maybe to find the Courier). The logs you'd unlock would be from research staff before the war talking about the warheads in hushed whispers and the final log by Ulysses, talking to himself like he always does.
Either way, there would need to be other eyebots roaming the Mojave (or at the very least, broken down in places) to provide a context for ED-E now that DC is no longer canon. Given their lack of armaments, they'd probably just be a civilian-oriented version of the Floating Eyebot for the first two Fallouts.
7. What about them being government-made? Wattz's contracts were beginning to get a bit too pricey for the US army's tastes so they started making their own (unfortunately sub-par) energy weapons. This way you could also have an additional tier of weaker energy weapons to justify the pistol in Doc Mitchell's house.
9. I'd just rather have it that addiction wasn't so easy to get rid of. Ideally, Doctors wouldn't cure you but they'd have you gather the ingredients for "Fixer" (which is now a post-war cocktail of disgusting things) and make it for you. Maybe you need to take several doses over time to make it work or maybe the scavenger hunt was enough work as is; either way, drugs would be more of a gamble and addiction-preventing perks would be more valuable.
11. Taking away the ghouls isn't necessary, just don't make them flash-ghoulified NCR soldiers. Perhaps a few straggler feral ghouls (or maybe even Endless Walkers) wanders in and takes up residence, attracted by the radiation. the area would also be a lot deadlier, making a radiation suit mandatory. So the mission is to wander into a deadly town, completely silent except for your own breathing; you wander in and out of buildings looking for the corpses of fallen soldiers while carefully keeping your distance from the rotting men and women who hover around you like ghosts, looking as if they're almost aware of their surroundings. You'd have to be careful of both the robotic defenses the NCR set up having gone haywire and not to get too close to the ferals who now will, just like in Fallout 1, only take offense with you if you invade their personal space.
15. The T-45 doesn't need to be changed. It looks like a prototype, which it is, so everything's hunky-dory with it.
19. I thought Power Armour Training was a clever way of limiting its use, but it could admittedly use a few more characters teaching it rather than just the Brotherhood.
20. The Sentry Bot from Fallout 2 and the one in Fallout 3 are different enough that hey can safely be considered separate models. Plus, I like the Fallout 3 one; it's one of the few things in that game that fit the setting.
I suppose, I don't know how to explain Vault 34 or what to do with it.
I was under the impression that ghouls are created only by radiation as it was understood in the 1950's and FEV has nothing to do with it.
Either way, the Vault itself could be rewritten for the most part.
I think that Vault 34 never had any FEV, the people transformed into ghouls by the extreme radiation leaking from their reactor after being damage by riots.
Vault 34 wasn't the best writing Obsidian ever made, actually it is really stupid to be honest. Here is another example: the Vault was sealed to prevent more dwellers from leaving, but the problem was that the vault was overpopulated... So the easy solution would be to let people leave until it wasn't overpopulated anymore.
But you forget that many Vault overseers had specific orders not to let people out until certain times, or were very paranoid about the outside world.
Either way, the people who left didn't leave due to overpopulation; it was because they weren't allowed access to the armory, and they eventually became the Boomers.
If having the ghouls there is the main issue, then that could be changed in a similar manner to Searchlight. Perhaps a firefight caused by a riot killed almost all the residents and the ghouls moved in later or perhaps when they decided to finally open the Vault door it was to a cave filled with ghouls and a malfunctioning sealed armory door meant they couldn't access their own weapons, leading to their demise.