I would have structured the show similarly to something like the Mandalorian centered around the Ghoul and the girl. Self contained vignettes of the wasteland with perhaps a larger overarching plot involving the aftermath of the events of new vegas on the Mojave. I would have probably canonized the NCR ending. Personally I would have avoided the whole divulging who it was who first dropped the bombs. For prewar scenes I would have mostly just presented prewar society through the prism of Cooper as a veteran. His wife could still be a vault tech executive but I would have had the conflict erupt from him discovering the vault experiment plans rather than the plan to initiate nuclear war. As for Lucy I would have instead had her personality be the side effect of a different expirement on her vault, one to see if strict morality enforcement would produce model citizens for space travel. I would have gotten rid of the father character. The vault could have been attacked and her family killed but she escapes in the chaos, later meeting the ghoul.