I think TES could really transcend the need for base dungeon filler enemies. Instead, I think it'd be a lot cooler if there were a finite number of npcs in the game world (who might change over time, traveling intermittently between cities perhaps), and that there was little actual incentive to kill the npcs, unless they were really psychopathic.
Suppose you play the game for five years, in that time you kill every npc in the game just for fun, or for quests, if you wanted to keep playing the same game with the same character you'd be living in a world devoid of life, we need npc's to generate randomly, if a house is unoccupied it should be rented by a randomly generated character or family who may generate random quests so you always have something to do even if you kill off the first lot of npc's. Npc's who are directly related to main quests and faction and guild quests should be unkillable (but you can knock them unconscious) until the completion of said quest at which point the npc becomes useless for further quests and can be killed.
The Dark Brotherhood or Camona Tong or Morag Tong, or whatever they come up with, should give you random npc's to kill and random ways and times of day and situations to kill them in, this way they never run out of things for you to do after you complete their main quests.
As a guildmaster or faction master you are given the ability to give quests to people in your guild, you'll have a room full of hopeful recruits you can choose from if some of your guild members die during your quests. You'll be able to choose from a list of quests to give your guild members at different levels of difficulty depending on how generous/cruel you feel. You can promote members once they complete a certain number of quests for you and at higher levels you can recruit them as followers. You'll have a 2nd in charge guy/girl who will give you reports on your guild members activities so you know if they have killed anyone or stolen, or broken the rules, and you'll know who has been behaving well. Occasionally your new recruits room will contain a spy from a rival guild, you may recruit them with or without knowledge of this and this will cause certain events to happen randomly such as an assasination of your guild members, an attempt on your life, the theft of the guild flag or some such. You'll be able to send spies to other guilds to be recruited who may either get in and send reports back to you or they are found out and killed or sent back to you. You will be able to send messages to your spies in rival factions/guilds to get them to do some things for you, either kill someone, rob the guild or steal the guild flag or some such, and they may simply steal supplies for you. There should be a budget system so that as guild master you can accept money from your guild members as joining fees and monthly fees, this can go towards buying necessary supplies for your guild such as food and reagents, weapons, spell research, books, etc.
You should be able to buy shops, or a shop, and stock it with all the rubbish you can't be bothered carrying around. Occasionally people will sell things to you through your shop which have some value such as rare books and materials, most of the time you'll just cycle through your rubbish and the rubbish they sell you. You'll always make a profit from your shop but you'll make less by stocking it with rubbish and more by stocking it with expensive and rare items, and by stocking it with expensive stuff you are more likely to recieve nice stuff when people sell you things. Things that are sold to your shop while you are away are kept out of the store inventory until you visit again and choose what to put back in and what to keep. You can hire a store clerk or two store clerks who are very honest, they will not steal from you, however your shop may be burgled by common thieves.
There should be more than one Thieves Guild, one guild you can join and do a main quest story and then the subsequent quests I've mentioned above, and another one or two independently operated guilds who compete with you. By having your agents in their guilds you'll be able to find items that were stolen from your shop or from other people, and you'll be able to track them down, say you wanted to get back a magic sword that was stolen from your shop, your agents found out that x guild stole the item, y guild had nothing to do with it, but later x guild sold the sword to mr calmly in reagent street, you go there only to find out that he was burgled in the night, your agents in y guild then tell you that they found the sword but it was sold to a mr angry in elbow close so you go there and you buy the sword back or steal it... etc. Oh, and by finding items stolen from random npc's by x or y guild you get the option of keeping it or returning it to the original owner for reputation or reward.
Stephen.