I'm running a D&D 4e campaign where the underlying story arc features Orcus and his followers. It starts with a run-in with a Cult of Orcus, and gradually escalates with the party finding that the reason that sort of thing keeps cropping up is because there's a plot afoot - Orcus, Prince of the Undead, is making a grab for power, and planning to march on the world of the living with an army of once-dead horrors.
I have a few story branches in mind for this, but one idea that I really like the sound of is for the party to repair the mythical macguffin that's supposed to prevent the dead from passing back into life (which is clearly malfunctioning because there's zombies everywhere). Of course, if they succeed in doing this, then they would have made it impossible for people to raise the dead... which includes the usual spells and rituals usually used for resurrecting slain party members.
I'd really like to keep playing in this world (I have way too much material to squeeze into this campaign, and there are some potential tie-ins that I think could really enrich future campaigns too) but I'm not sure how well a game would work with actual permanent death. I can avoid using zombies and the undead (there are plenty of monsters to choose from, after all) but I don't know whether it's a good idea to not let the players resurrect their fallen characters when the rules say they should be able to.
If necessary, I could compromise and say that when a character in combat reaches a state that the rulebook would call "dead" they're actually just mortally wounded, unconscious and beyond the reach of any healing that can be given in a combat situation, and then re-skin the "resurrect dead" spells as "heal mortal wounds and revive from coma" to bring them back when the fight is over, but that makes the characters essentially unkillable, and removing the fear of death from the campaign is something I'd definitely like to avoid. I'd also like to avoid reverting or circumventing the no-necromancy restriction too soon, because I think it would cheapen the party's actions - if they can see the impact their actions have had on the world, it'll feel much more epic for them. (Also, it'll be more terrifying when I pull out zombies for them to fight sometime way in the future, prompting a campaign where they have to find out who's found a way to raise the dead again, and how to stop them.)
Could a game like this be made to work?