Varying resistances!
e.i:
Creature resistant to damage from weapon not made from a specific material.
Creatures immune to damage from weapon of +2 enchantment or less.
Damage reduction like resist Fire 5, Ice 10 etc
and bring back the old energy types:
fire, cold, acid, lighting, arcane, negative, divine (sacred? positive?), sonic
Maybe go back to poison and disease draining an ability score.
For a bigger change, I'd go as a far as suggesting as to remove Concentration. Pre-buff like there's no tomorrow, baby! BUT....I'd give AoO for casting spells in melee, and spell disruption on a hit.
Also, AoO for every reason possible: moving more than 5' without disengaging, standing from prone, shooting in melee, using an item in melee etc
Varying crit range and multiplier are a fun idea, maybe just take the weapon/armor chart of the 3.5e PHB? No need for crit confirmation, those were dumb.