All encounters are no longer leveled, the appearance of a given NPC or creature only depends on your current location and luck.
Some creature encounter lists have been altered, for example you will see more small than large mudcrabs and more wolves than bears.
Loot is no longer dependent on your level, but high quality items are of course much rarer.
Quests rewards are decoupled from your level.
Locks no longer change, a master lock at level 1 will always be a master lock.
Trap damage is now independent of your level and therefore much higher and often even lethal.
Your enemies are more skilled than before. If somebody wields a mace, you better expect some armor crushing blows from him.
Weapon damage has increased significantly, especially archery, which is now deadly. A skilled archer can frequently take out an unarmored humanoid with a single shot. But drawing a bow now also takes considerably more time.
Blocking and/or dodging is now essential if you want to survive melee combat.
Dragons are the flying, magic casting tanks with teeth that you should be afraid of.
Dragon priests are even worse.
Weight of your armor affects your magicka pool, clothing is better for mages, Spell sword is not something to be at level one, either focus the sword or the spells.
Don’t expect to be wearing heavy armor and running marathons from level 1. It takes perks, time, and training to master the art of being a walking tank.
Heavy Armor makes sneaking impossible.
Sneak mages can’t exist. Spells Make noise to cast until you are deep into the illusion tree.
Stamina is a precious resource at lower levels. Wearing any armor without the first perk causes a drain standing still, even with the first perk you will lose it if you are running around. Anyone with armor should be investing in stamina restoration food.
Some quests have had starting requirements changed to accommodate for the rewards, no more doing daedric weapon quests at level 5.
Survival has a much, much greater importance, you can and will die if you don’t eat, sleep or stay warm.
Your initial Carry weight is more realistic, but you can craft or buy Backpacks to increase it.
It’s dark when it’s supposed to be, night vision, a torch, or lantern is required for dungeon diving.
Getting sick and/or drunk and/or consuming a lot of alchemy ingredients gives a visual effect/blurring on your screen.
Food is essential - the perks they offer to regeneration alone mean you should always have a buff active
Houses have had their prices or quest requirements altered.
Blacksmithing and enchanting are no longer mandatory, blacksmiths and court wizards can do these services for you.
Level cap is 82, therefore Perk points are limited. Plan where you are going to spend them accordingly.
Vampires are Allergic to sunlight, and restoration spells don’t work. They have their own healing spell in the conjuration tree.
You are not forced to perk into lock picking. Spells for unlocking, scrolls for unlocking and just plain smacking the lock can be used instead.
Aedras (good gods) don’t like crime; you make crimes, they turn their back to you and prevent shrines from functioning. Once lost, you cannot regain the blessings, however there’s a legal way to get their “cure disease” back, but honestly is not worth the penalties it inflicts.