I don't really know if it is a direction you wanted to go toward, but as you mentioned that we would be able to turn into ghouls or super-mutants, it got me thinking on how it should be able to impact the gameworld.
For the super-mutants, it should be both hard and easy. Basically, most settlements should turn hostiles, as there is no sign of peaceful integration of super-mutants at that point of the timeline. The exceptions should be Necropolis (barring Set's group), Mariposa and the Cathedral (barring Laura), and the already invaded locations. But that would also mean barring dialogs with the Master, the Lieutenant, Morpheus and any talking head that would want to dip you, and maybe change a couple of dialogs with npc that were initially supposed to prevent you to access some areas. And those who talked to you like you didn't know anything about the Unity. And maybe add one or two npc that would actually provide more dialogs. So easy solutions for most areas, but a bit more works in the remaining ones.
For the ghouls, i had hoped that we could barely change anything in the main quest, while giving you a reaction penalty with everyone, and making hostile the talking heads that would want to dip you ( and make the BOS hostile as well). But after making a couple of tests, it turns out that the
reaction system is barely used in the original Fallout (it has a lot more impact in the sequel, especially reputation an charisma). It made several tests, each time piling up penalties over penalties, and it didn't seem to change much of the dialogs and initial reaction. 1 charisma, 20% speech, child killer, wanted, wanted for murder, wanted for thief, didn't change anything. -1000 of karma and berseker seems to make an handful of people midly distrustful, barely more than James after you blow up Megaton, sometimes calling you a raider, but stilll proceding with the rest of the conversation. It was more a bonus for bad guys reaction than a malus for good guy reactions. Out of desesperation, i ran a test with intelligence. They DO have a very different reaction, but only AFTER you've started talking. So, not much luck with initial reaction.
So ultimately, unless we would do an extensive recoding of the npc reaction system of the original fallout, they would be no easy-to-implement default reaction to a ghoul. At best, what could be done is rewriting a bit a couple of npc, where it would make sense, (a bit more work at vault 13) so it would feel like the transformation made a difference, while considering that 99% of the npc wouldn't make a big deal out of it. I could investigate which npc would probably have to change a bit, if it is a direction you want to go toward.
