I just watched your video, and damn, you do describe a VERY interesting Fallout. One that would be ambitious and very, very costly, but actually possible. Congratulations for this amazing video, that should be watched by Bethesda.
You mention the possibility of being sick, and need a cure, as a motivation for the main character. I had the same idea, and I think it would be the best way to reintroduce a sense of motivation, realistic urgency (one that keeps you going, but still lets you explore and do some side quests) and it should be a way to bring back a timer. You have six months to live if you don't find a cure, or something similar.
We could even dream wild and imagine a mechanic where you'd infect people you spend too much time with. Some factions want your blood, to weaponize it, to study it, to find a cure... Give it to them on your own will (which should bring down your stats but boost your reputation with said faction) or resist. Your choice.
In the old Fallout way, getting cured should only end the first act, and has little to do with the actual, real threat that will be unleashed at this point, and initiate the second act. Have your personal, selfish quest turn into a heroic tale, as you get into the bigger picture and start to fight for something other than your own survival. Think about "soul reaver" kind of narrative. In any case, the actual, real antagonist shouldn't be the one responsible for injecting the virus to you, it should be something way, way bigger. Something EXTREMELY sinister and creepy. Don't be afraid to go dark. It needs to touch the absolute horror of radiation. It could be an evergrowing biomass coming from underground, releasing walls of spores, worshipped by some apocalyptic tribes and cults etc, for example.
Quite a big quest could also be centered around a vault getting ready to wipe the wasteland clean in order to protect its citizen from the factions who want to get in, using a chemical weapon. Organize a siege or act as an ambassador to find a compromise, but whatever lies within the vault needs to bring a feeling of horror. "Icy" had quite a similar theme, and damn, it worked perfectly. "Vault rangers" should be a thing. Blue/Yellow hazmat suits, heavily armed, hostile to almost everyone, paranoid looters searching for "something" outside, even sometimes kidnapping people. A creepy alternative and a new take on the vault visual theme, that should surprise players.
Taking over the vault should bring about a HQ/Base mechanic, like in Pillars of eternity. But it should be a reward for the second act. Many RPGs tend to introduce that sort of safe zones too early. The settlement building system should be earned the hard way, if kept in this interesting concept Fallout of yours.
When it comes to the character's identity, I think there should be one available, one that is original : "you are a reporter, documenting what's happening in this part of the wasteland." your camera acts as a weapon that deals zero damage, like in "Beyond good and evil". Aim and shoot to take a picture. You now have a very clear reason why you should get to the frontline and speak with everyone : you need to have visuals and interviews. You have a clear motivation for a pacifist playthrough, BUT you can also be a ruthless war reporter who doesn't hesitate to take arms if needs be. And you can tell the tale in different ways. You can take sides, with your words and your pictures (the Piper interview scene actually showed how easy it would be : simple dialogue options). Imagine how it could have shifted the narrative from Fallout 4 (will you show the Institute as the boogeyman they are, with pictures of synths tearing down cities and kidnapping citizen, or will you speak of them as the misunderstood saviors that need to be helped? Will you make the commonwealth resist the arrival of the brotherhood or will you depict them as saviors?) That's actually a totally new way of handling the karma system, one that should be, at least, considered for a sequel.
Bring the loyalty/fear mechanic from Tyranny. And near the end of the game, make your companions speak on your behalf, judging you, and depending on their testimony, have a final situation resolve differently.
There should also be, at least, two very clear resources at separate locations. Which would explain the caravan roads, the faction infighting and the presence of, at least, two major settlements (think about gastown and the citadel from Mad Max, for example).
—and immediately derided by TES fans looking for a new Wasteland-TES game.
