From what it seems, only main quest givers will probably be the only immortals, that and children.
The problem with Morrowind's way on the main quest is that people can ruin their entire game save by accidentally getting to an auto save point right after they killed an essential NPC. Also, the last save could also have been in awhile ago and then you kill an essential NPC you didn't know so you have to redo everything you already had to do, so you just threw away 10 minutes for nothing. That is really annoying and having a handful of NPCs that can't be killed until after they are of no more use to the main quest isn't too much to be asked.
From what I understood, one of the main reason for the inclusion of "essential" tag for some quest-related NPCs in Oblivion seems to having more to do with the fact that most NPCs were assigned to a unique schedule, where some of them regularly travel from one city to another all on their own. One example is this incident related to "A Rat Problem" quest line in Anvil. There's a certain essential NPC involved who sometimes making a trip to Chorrol and back on her own once in a month. Had the essential tag absent, she might end up killed by the hands of trolls or other hostiles when you were NOT EVEN PRESENT at the crime scene, so to speak, as it all processed in the background. This is actually occurred to my play through, as my PC casually walking through the forest was greeted by her limping corpse just nearby Greenmead Cave. But since the quest itself was already finished by that time, there's no worries. Now imagine if the essential status weren't there, and I haven't even started the quest line; it's not my fault that she ends up dead and the whole quest line failed to launch!
It all depends on to what extend the Radiant AI can help to alleviate this issue, methinks.