That actually sounds pretty easy to do in and of itself, though of course agreeing on how to do all the supernatural shit (and actually implementing it) would add a lot more work, unless it was only trivially different from the mundane stuff, in which case there wouldn't be much point to it...
A setting slider in the game options would be just super if it's feasible. Yeah, I guess most of the hard work would go into implementing the vampires in the first place, and making the game not use them if the option isn't set would be easy.
Perhaps not a slider per se, but a few different options would probably be easy, if each used a different list of what to spawn/drop. So long as all the item and npc type definitions (and basic PC template(s)) were stored in special files, like df's raws.
So, say, a "Realism mode" list would have mundane items and regular humans, with the luck stat set to whatever level wouldn't give a bonus or penalty in whatever it does, specifically, while an "Action movie" one would also have mundane items and regular humans, but luck would exist, and there may be some ability that allows you to burn/temporarily deplete luck (or some other stat based on luck and modified in various ways by one's actions, like being increased by pulling off something difficult without using/with minimal use of the points) to survive/avoid grievous injury, or retry an attack/skill check (I'm inspired specifically by Dark Heresy's fate points here, though I seem to recall other RPG systems having comparable points). A "Light fantasy" list would have minor supernatural things, as very rare and unexpected encounters, along with (optionally?) what was found in "Action Movie" mode, perhaps even to a stronger extent (more extreme luck stats, more powerful options for "fate manipulation" stuff). And "Urban Fantasy" might have vampire crime families a la VtM, zombies in the sewers, mages of some type or another, that sort of shit.
Of course, at higher levels, you run into much more variety in what could be done, and it's a lot more content than would be in the basic mode, so I would say to more or less ignore that end of the spectrum initially, but try to set things up so that one could choose to use a specific list of items/npcs to allow work in that direction in the future (and leave it easily modable, as a bonus).
Basically, I mean that the mechanics of the game would always (once implemented) include both the basics, and special, supernatural abilites, but in order for the supernatural abilities to ever appear in the game, there would have to be something in the raw file that's being used that has the ability, like an "UNNATURAL_LUCK" (for a "spend luck/whatever to retry a skillcheck" sort of ability) or a "BURSTS_INTO_FLAME_IN_SUNLIGHT" tag.
I'm on the side of location based damage, and a more complex inventory layout. Thus, placing things in pockets, pouches, packs, but also an idea of straps/belts, like you'd get with some guns, or on packs, and needing one's hands free to use an item (perhaps a coordination check to accomplish simple tasks with your hands full?), perhaps even allowing for multiple items to be carried at once (think a bundle of something, or a precarious stack held between one's arms and one's chest), along with a fuzzier encumbrance system than "59.9 weight units and you're perfectly fine to run a marathon across the city! 60 weight units and you can't budge an inch, or have trouble walking across the room (lol STALKER),".
A really complex inventory layout could both help with immersion (I have this knife in my right jacket pocket and I can take it out this quickly), and hurt it. (What do you mean, "no free grasp"? Just pick up the fucking knife!) The inventory should be easy to manage so that it doesn't ACTUALLY become an annoying puzzle you must wrestle with every time you pick something up. Try playing a game of DF Adventure Mode without a backpack. It's terrible. There should be plenty of ways to carry items (like bags, backpacks, tool belts, pockets, holsters etc.) and the item size and volume restrictions should be fairly lenient. And maybe letting you carry an unrealistic amount of things in your hands, so that if you just want to grab a shitton of stuff and haul it to the other side of the room without worrying of things like stealth and acrobatics penalties, you can do that easily. Giving a lot of really small movement penalties for carrying everything might be good. Having any amount of weight on you starts slowing your running speed, but you can still walk normally with a heavy load. And if you're carrying something weird where it's visible, people should get suspicious.
Personally, I'd err on the side of realism for the inventory, and just try to make potentially annoying tasks easier, and then refine/fix problem areas once it becomes apparent where they are, rather than starting small and slowly making things more realistic, where you'd be adding potential problem areas rather than just fixing them.
Speaking of taking knives out quickly, what're we planning to do with time? It might be cool to have things like western-style gunfights where the winner is the guy who draws faster.
Technically the guns they used couldn't hit the broad side of a barn at the ranges such duels would take place at, so speed had essentially nothing to do with who survived...
Would it be worthwhile to separate the actions of drawing, aiming and firing a weapon, so that spraying a magazine of bullets vaguely to the right direction would take next to no time, and pointing the bloody thing at the target would be the involving part?
Well, probably the longest action there would be bringing the gun up to where you could aim from, since, in my experience, the actual aiming part (unless going for careful precision) is rather brief and automatic. Of course, if you don't want to make guns realistically OP, you'd have to gimp them somehow, and that might be one place to do it... On the other hand, in a "Realism mode", you might well want guns to be devastating weapons they are, with their downside being the volume and possible illegality...
If an experience point system would be used we wouldn't be leaving the stealthers in the dust. Exp would just be provided for completing goals instead of just killing someone. So if you were assigned a job to get some piece of art, it doesn't matter if you kill everyone in the museum, sweet talk your way in, or just break in at night, you'd get the same EXP. Also probably would need a way to get XP from minor milestones throughout the game to keep it from being 100% mission based.
If we do a skill based approach where skills improve with repeated use I don't want it to devolve into sitting in a corner picking and relocking a box to improve skills. Grinding up skills is something for MMO's. This is supposed to be fun. Paying a trainer seems fine, but what are the limits? Is it just money? Time? Some artificial level limits? Rarity of trainers?
Unless we can find a really good way to prevent boring skill grinding I'm leaning more towards applying XP from goals.
Perhaps a mixture would work? You gain specialized experience for using skills, and some percentage of that as generic experience, and then have the option of leveling a skill either with generic experience, or with specialized, perhaps giving an option to convert specialized into generic at a penalty.
Or allowing a sort of auto-grind, where you just set it to a task for a certain number of in-game hours/minutes, and then it just rushes through that with no interaction from the player, though of course that could only be done for so much of the time, and you'd have to spend the rest of the time working/sleeping/whatever. This would be like practicing picking a lock, moving quietly across a floor, using a firing range to practice aiming (though that would cost money for ammunition), etc.
Trainers can only get you so far. I can see meeting a professional locksmith and getting up to 40-60% (Assuming a percentile skill system for the sake of an example), but after that you're going to have to go out and practice on real locks.
How does this stop me from having to grind away somewhere safe just picking locks to improve skill. It also makes some skills absolute nightmares to level up. We also get a situation where with things like sneaking where the player just turns on sneaking and sneaks absolutely everywhere. Then to counteract this the skill improvement rates need to be lowered, forcing legitimate players to have to grind their sneaking skill.
Sneaking is a suspicious activity, and creeping across a street in broad daylight hunched over shouldn't really count as "sneaking" to begin with. Stealth shouldn't be a "stand in the middle of a brightly lit room, completely invisible to everyone, just because you have 1337 sneaking skills", and should be more a mix of perception (determining where things that could see you are), ability to move silently (so as not to draw unwanted attention), remain still and silent in hiding (so as not to draw unwanted attention), and detecting places to hide (so as to have some place to hide).