I leaned heavily on two-hand for ahwile, because I had this kickass glass greatsword and Molag Bal's Mace. But now I'm leaning on the Blade of Woe (since it levels up with you, if you're DB), so one-hand is on the rise. And, of course, the always favored restoration skill.
I've also been trying to focus on lockpicking and light armor (since, again, I'm wearing the DB ancient shrouded armor).
I've ignored smithing and alchemy... mainly because it came so naturally in Oblivion. I guess I'm having a hard time realizing that, now, you actually have to pay attention and master shit as opposed to buying 100 hammers and stealing a mega alchemy set and killing time when you're bored.
It just feels like I've hit level 21 and I'm a sad joke who gets raped repeatedly by dungeon bosses while my companions cower in a corner and/or muse about the weather.
Then, limping around outside, three bears lunge out from behind rocks and just hammer me down like a whack-a-mole.
I've also managed to perma-kill all the companions I like, thanks to my tactic where I run away and leave them stranded somewhere fighting a clan of master vampires.