I would HATE to be forced into a box like that. Automatically having the majority of NPCs in the game world react unfavorably to the player would be really unenjoyable.
I personally hope Obsidian follows the example of Project Beauty and things like the Saram hair mod and puts those in New Vegas. No reason not to, and it'd make the game way better.
i dont' understand why it wouldn't be enjoyable. it would be realistic.
And that also falls under the assumption that the majority of the game would take place amongst non-ghouls.
Say it takes place in new york, and the majority of urban NY is basically a huge ghoul city, or perhaps underneath NY in the subways and sewers. And the suburban area is populated by human factions trying to take control over urban NY. I think it would be a welcome change when the ghouls are the ones with the advantage with location, weapons, and population numbers.
I'm still curious as to why people are so adamant against any sort of specific focus when it comes to the main character. To me it makes the world around the character more responsive and realistic.