Difficulty 100: Obvious one, some people still find it easy.
Dead is Dead: If your character dies, he's really dead. Start a new character. You'll be much more protective of your character if you only give him one life to live. Still save though, since the game is prone to crashing.
Map Begone: Don't use your map, and very little of your local map. Go by landmarks and directions throughout the whole game.
Flip your Skills: Make the skills you'd usually make Major, and make them Minor, and vise-versa. This will make your favorite skills harder to get good in, adding a new experience.
Play Naked: Play the game with no armor, or unamored skill. Popular choice, since armor really does help you out in the long run. If you must, you can play with clothes. But what fun is that?
Mods: I don't know of any mods that make the game harder myself, but you can check the mod forums, they usually have good suggestions.
Rocky: Go through the whole game only using Hand-To-Hand. Assuming you don't use mods that make it damage instead of fatigue, this will be a challenging pace. Though you can laugh in the face of a fatigued Daedra.
Pacifist: Don't fight or kill anything, unless you're required to. Players using this playstyle will want to increase their speed and athletics as much as possible. If you have to kill someone in a cave for a quest, don't kill anyone in the cave except that person.
All in one: Combine everything listed above. Make your character a one-lived, mapless, minor skilled, naked, hand-to-hand using pacifist. If this is STILL easy for you, then