Master difficulty, No weapons, No armor, No smithing, No alchemy, No enchanting, No followers, No perks
(Full disclosure: No followers except when dictated by quest, and I did disenchant/enchant ONCE just to make gloves with fortify unarmed to make brawling plausible on master difficulty.)
Notes: This is hard. Conjuring a distraction is a necessity for even moderate fights, and destruction magic simply doesn't have the offensive power to cope with tougher enemies. Dragons are a "run for your life" scenario unless in a town or other guard populated area. Animal ambushes in the wilderness are deadly at lower levels, and potions quickly run dry. Riding a horse is the safest defense strategy for travel. Bandits and thugs in groups are very difficult, and higher level spellcasters are brutal even with 40% magic resistance (Lord Stone + Agent of Mara.)