Instead of having Essential NPCs be immortal, I suggest implementing a Hospital into towns and cities. Then when you shoot, or "kill" someone who's important to a quest, you don't have to even get a notification that they are quest important, when the time comes, you will simply be sent to the hospital or to their home and learn that they are at the hospital. I guess that won't really make them less immortal, but it will make it less striking.
In any case, I would actually like a Hospital Faction, where quests can consist of getting sent out to people who've been injured, as well as helping the city guards, and cure deceases.