To continue from last time a bit here's how I see locations should "equate" to a instant kill:
Dieing is pretty much simulated by blood loss (your health), every hit that breaks your skin means you bleed, the larger and deeper a cut is the more severe it will bleed. Most smaller injures don't bleed much and even stop bleeding on their owns, really large ones need to be bandaged or treated in some way, they close on their own too but here you could bleed to death before it closed enough.
A main artery bleeds very severely causing fast health loss, the main leg or upper and lower arm arteries could be lethal within a few minutes, the main neck arteries lethal within seconds, it's not instant in that case but it has another effect, a shock.
A shock can knock someone out cold, it can be caused by severe pain, a very rapid blood loss or a brain injury, your fatigue in that case doesn't matter.
A hit in the heart isn't a real instant kill, it still at least takes a few seconds to die, however it will in most cases cause a shock that sends you down making you unable to act and maybe "fix" the wound in time. When you're more "hardened" so to say you CAN shrug off a heart injury without being KOed, you still have to take deal with a severe bleeding (a internal one to boot) but it makes it possible to survive that.
A brain severe injury sends you down as well but again it has to be sufficient enough, a arrow to the head is not necessarily lethal if it didn't penetrate too deep, but it too causes a severe bleeding and can knock you out cold. Survivable brain injures can leave the character extremely weakened and weary even causing skill "damage". If a arrow really penetrated deep it is too not really instantly lethal but within seconds and causes a shock that sends you down.
It pretty comes down to if you're knocked out and not really able to act anymore you are A. a vulnerable target and B. not able to fix potentially lethal injures which then cause your death.
One other route though is suffocating or your heart stopping (from a strong lightning bolt for example). Suffocating would drain your stamina, not your health, when your stamina is down you're KO as well, if whatever is suffocating you continues it's counted as brain damage, that means if it lets go in time you CAN get back up although with some damage that needs healing.
Your heart stopping would go a similar route, when it stops your blood is not pumping anymore too resulting in your fatigue draining, brain damage and ultimately death.
In fact blood loss can be equated to that too, when you lost too much blood your brain stops working and you die the same way.
Like this you pretty much have ALMOST instant kills but there ARE saving throws so to say.
EDIT: I just came up with a new idea to include another value, "Vitals" for brain activity. I'm still working on that part so I can't give too much details but I'll try to write it into a coherent idea.
This is all far too complex. What is the huge problem with the methods TES has used from Arena to Oblivion? It has always been pretty much the same, with minor changes, and there's no need for "arteries", or "brain injuries". Bethesda should stick with what they know in TESV, and not end up giving us a huge facepalm game. If anything, the only changes should be stuff they've worked on with other games. though, even that could make it not a TES game. I mean, sure, at certain times there should be variation between the games, but the actual gameplay methods shouldn't stray too far away from what we all know and love.
Pretty much all that should be considered in these threads is the widly accepted ideas; Lycanthropy, more skills, more lore, unique terrains, etc, etc. What we should do here is throw out small ideas that seem good, and see if it's something that the majority of players would like to see. Not come up with silly, over complicated systems that can let me kill someone in one hit.
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What I'd like to see is a more static levelling system. But, to stop me getting god like too early, there should be more defined areas. A level 1-10 area, a level 11-20 area, a level 21-30 area, a level 31-40 area, etc, etc. It lets my character aways be challenged, but lets me go back somewhere and feel my progress. Also, I should eventually get the god like feeling. But only around the stupidly high levels (60-70). This is pretty much Morrowind's system, but more defined, and suitable for higher levels also. It would need a larger map, so my level 1 doesn't accidentaly wander into level 50 territory. It also gives great purpose to paying for fast travel.
I'd like to see scaled wildlife. If I see a low level wolf, it would be around 70% scale. If, on the other hand, I saw a high level wolf that'd rip my low levels heads off, it'd be 2x scale. It makes the enemies seem more frightening to be larger, and would give the right feel to the game.