My opinion depends entirely on what hardcoe has.
Things I'm in favor of:█ Diseases
█ Instant Fast-travel locked
█ Serious Injuries (Think Diseases, except a chance to process when you take a Power Attack)
[figured I'd elaborate]: Debuffs applied to the player for, what essentially amounts to poor choices in combat. Can only be cured by powerful Restoration or master alchemists at apothecaries. Adds higher stakes to encounters, especially for encounters with lower-level creatures/people.
Examples:
?Fractured Wrist: Reduced Critical Chance.
?Dislocated shoulder(L-R): Reduced weapon/block effectiveness
?Severe Laceration: HP Reduction
?Concussion: Decreased magicka regeneration(if applicable)/reservoir (if not.)
?Blood Loss: Increased Stamina costs and reduced Stamina regeneration.
?Mortal Wound: Damage Over time
█ Reduced Healing(item) effectiveness (Stimpac Nerf in New Vegas)
█ Reduced Skill XP gain. (Not reduced XP gain, since that would effectively lower your theoretical cap)
Things I could take or leave:█ Basic "Needs" (Food, Water, Sleep)
█ Additional Inventory Burden. (Works in New Vegas better because of Ammo)
Things that Seem more trouble than they're worth:█ Prolific Environmental Hazards (Cold).
█ Any ridiculous "needs". (Defacation/Urination)
█ Anything that imposes a Time limit on the game itself (Aging)
Given that I play every game on Easy and usually in God Mode, I'm going to go with "no" personally, but it's a nice idea for those who want it.
Easy
and God Mode? You might as well read a book, they don't bite!