I would love to see more realistic diseases being implemented.
In oblivion vampirism (polymorphic hemophilia) was treated as a real disease and it had consequences and that sort of thing. I thought that was a great idea, but I didn't like the limitations of the disease.
Combine these ideas with the great AI tweaking idea brought up by That One Guy because honestly there is no reason in the world for Bethesda to not implement it:
Dredging up an old post of mine from several months ago, here's what I envision regarding actually putting the "Radiant" in Radiant AI, and AI that factors in fuzzy logic:
Well, the first step towards a more coherent AI system is to give guards the ability to take NPCs to jail. That way, petty theft doesn't get punished by death, and punishment by death doesn't lead to factional revolt against impossible odds.
The second is to incorporate some form of desire versus consequences scale for actions, with numeric thresholds determined by AI personality settings to decide when certain actions are taken and certain actions aren't. For example, City-Swimmer gets caught stealing bread. The nearby patrolling legionnaire attempts to take her in. City-Swimmer numerically evaluates her chances of survival by resisting arrest (guard's skills and attributes versus her own), the accuracy of which is determined by some skill/attribute based perception algorithm. Then, City-Swimmer's evaluation is compared to City-Swimmer's aggression rating. If her aggression is high enough to offset the the chances of survival (assuming the chances of survival were evaluated as low), then City-Swimmer could resist arrest and attack. The legionnaire would then pummel City-Swimmer. However, this doesn't have to mean death. The further the percent of City-Swimmer's health drops, the closer that percentage comes to overriding City-Swimmer's high aggression setting. And when it gets low enough, City-Swimmer will yield. The legionnaire will then evaluate whether or not to accept that yield based on his responsibility setting, which, for a guard, would be pretty high (meaning he'd let her live and cart her off to jail). That's the huge gaping problem with our current AI setup. It's all or nothing, and no room for in between or dynamic decision-making based on constantly-changing outside factors. But the outside factors aren't too terribly difficult to add in.
This would apply to a multitude of situations, as well. For example, Bethesda cited the residents of Bravil's skooma den as a good example of why they toned down RAI. The skooma addicts were given a desire for skooma. And there is a skooma merchant just across the way. However, the addicts have no money for skooma, yet their desire is their sole focus, so they promptly would go kill the skooma merchant to satisfy their given desire. All or nothing; fulfill at all costs. With the system above, the skooma addicts would evaluate the consequences for murder (perhaps by developers pre-assigning specific actions and parameters with numeric values to indicate severity of consequences). Then, the numeric strength of their desire for skooma would be weighed against that numeric evaluation of consequence, as well as responsibility settings. If their desire wasn't strong enough to outweigh the consequences, then they'd refrain from murder yet still retain the desire for skooma.
That's the basic form. If we added in the possibility of desire increasing as the amount of time passes that it goes unfulfilled, things would get more interesting. Not to say that all skooma addicts would reach the point of desire where murder would be justified for them, but some would (dependent upon AI personality settings) Further, if we added other options to achieve the goal of skooma, that would increase the interesting factor. Skooma addicts need money to fulfill cravings? Then allow for NPCs to find scripted freelance work around town, odd jobs and what not. Whether those jobs are the more traditional and legal sort, or the slightly questionable sort, depends on the NPC and the AI conditions for hiring. The job itself, visually, wouldn't be more complex in nature than having two or three lines of dialogue, and a few "go here" AI directions. Everything else would be happening behind the scenes. And with their newfound money, the skooma addicts could feed their habit and sink themselves back into poverty, thus necessitating the repeat of the process.
So here is my disease wishlist (haha):
1. Diseases should affect social standing. Diseases should add traits to any NPC which has the disease (including player). Depending upon the diease, other NPC's may treat them in a certain way. So if someone with leprosy walks into a bar where the general populace is afraid of the disease they may say "We don't serve your kind here Leper! Get out!" and if infected NPC (or player) does not leave the guards will be summoned. I realize in Oblivion if you had vampirism and people saw you the personality point score would decrease... In a world where people are terrified of vampires I would have to think they would be more likely to call for the guards rather than make you pay full price for an item.
2. Diseases that turn you into a monster should really turn you into a monster. So if you contract a werewolf disease, whenever there is a fullmoon you should turn into a werewolf (obviously). But what then? You just walk around slightly more hairy than before and thats it? How about making it so every NPC you see appears to you as an enemy, that way you are more likely to attack someone just like a werewolf would be.
3. NPC's with diseases should act accordingly. If an NPC contracts a disease like werewolf disease they should go mad and attack others as well (possibly spreading it).
4. How do we keep whole towns from being overrun with disease infested monsters? Those who are faithful can pray at the church and be cured. So while terror may reign for a night or two the balance would be kept. Plus the guards would be able to dispatch a werewolf or vampire relatively quickly. The biggest concern would be for stray people out in the wilderness (which is more realistic.)
5. Items that are powerful against diseases should always maintain their potency. If an NPC contracts werewolf disease but carries a silver sword during the day it looks stupid as hell. The NPC should drop all the items that they can't stand. Also attacking them with these items would deal additional damage.
6. If this system were in place the role of the church/healers/shamans would be increased, a player could make a lot of money (and have a cool story to play out) if they played as a travelling shaman going from town to town healing the afflicted using herbs and plants they find along the way.
7. There should never ever be a cure diseases potion. It devalues the importance of diseases in the game. If you could just cure it by drinking a simple potion then you really don't care if you catch it or not. Each disease should be treatable by a unique potion specifically made to cure it. The other way to cure it should be through divine means, through a powerful priest or healer. Therefore cities and towns become bastions of healthy people whereas wilderness areas and villages become much more risky.
8. The disease system should work seamlessly even without player interaction. People with vampirism should only come out at night, people who are werewolves will try to avoid being out at night. Diseases should spread and be cured through NPC actions on their own. It should be programmed within the AI.
Basically if you are going to make an open world like oblivion was where everything runs on its own you need to put in place systems that affect all things. It should be integrated into the decision making of the AI: diseases, economy (money, jobs), personal needs (sleep), wants (jewelry), factions (race, guild, town, nation), negative and positive consequences.