Here are my house rules:
*** DEAD-IS-DEAD --- I play all RPG's no-reload, from Icewind Dale to Diablo to Dragon Age. If a game isn't balanced for this I don't bother playing it. In Skyrim, I have lost over 300 hours of gaming and a dozen characters because of this: if my character dies I'm dead. Then I put away the game for a few days, even weeks, and come back after the grief period and start a new character. I have yet to 'finish' Skyrim even once after a year of playing.
*** No munchkining --- basically, don't abuse the system: no grinding skills, no repeat castings of spells for no reason, no thousands of enchanted daggers to level crafting, no abusing path finding to kill giants etc.
*** Role Play --- pick a theme, goal, character type and stick to it --- if I am a goody two shoes paladin type I won't break & enter people's houses; I may rejects quests from Daedra etc.
*** No Fast Travel --- Carts are okay, though. I also use a Mark&Recall mod, anchored at my home, and utter "thereisnoplacelikehome" whenever I want to get back home quickly. Otherwise, I walk everywhere.
*** mod use --- only mild changes that enhance immersion:
- Frostall & Realistic Needs for dealing with cold, wetness, hunger, thirst, sleep (I use timescale=10).
- Realistic Lighting for darker dungeons.
- Resilient Dragons -- more staying power for Dragons without altering them too much
- Potions take time -- I have the mod that gives a duration effect to potions (e.g. 5 health for 5 secs, non-cumulative, instead of 25 health instantly). So, strategic use of potions becomes essential for survival. You will pay for good potions if you want to live!
(Most combat mods or no-leveling mods are not dead-is-dead friendly and assume that you will be repeatedly reloading anyway because they are not well balanced.)
With the above settings the game is a significant challenge from the start. You can't explore far north or you would freeze to death -- even an early trip to the Bleakfall ruins is perilous, especially at night. You won't go into random crypts or dwemer ruins unprepared without the dread of death. You will be reluctant to do major quests too soon.
Levels 10-20 are actually very dangerous because enemy difficulty increases faster than your resilience. I always travel with a companion and I am not above running away from difficult encounters. (If my health is down to half I consider myself in imminent danger of dying and hightail away immediately.)
In my current run (level 26, Breton, Dwemer Scholar) I came close to death within a sliver of my life bar three times. It paid to invest most of my level ups into health and playing very cautiously.
*** BOTTOMLINE: This game is surprisingly well balanced at Adept difficulty (including the oft-discussed Destruction skill) for a dead-is-dead run. For most encounters you will be overpowered as the growing hero that you are, but if you act foolishly you will likely end up dead sooner than later.
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For those who are curious, here is my current character:
Akhaneth Suncloak
Breton
Father was a Nord knight. Mother was a Breton sorceress, slain by vampires. Akhaneth was a personable, yet reclusive scholar of Dwemer Lore, coming to visit Calcelmo of Markarth for further study of Dwemer Ruins. After being dragged into the civil war conflict at the border crossing and the coming of the dragons, he has turned his interest into practical matters and martial training. He is an apprentice craftsman of Dwemer artifacts and has recently pledged his skills to the cause of the returning Dawnguard -- finally there shall be revenge for mother.
[build: major: Heavy Armor + One handed + Block + Restoration + Destruction / minor: alteration, crafting skills]
Currently level 26 with 330 health & 160 magic. Smithing dwarven items only and enchanting them, also for my followers. (My echantments are actually not as good as what I find during adventuring, but I can choose to wear Dwemer only items. As a house rule, I will not abuse enchantment. I also cannot use more than two enchantments of the same type at one time: so, no zero-cost spells.)
Akhaneth hopes to stay live and see this grand adventure through to its end...