lol @ sheep saying Anivia is "hard to play." When in fact she is one of the easiest champs to pick up, and if you have a fraction of a brain you can do fine with her. And if you can't, it's a failing of you as a player.

Real hardest character to play...probably Karthus. main form of damage is a tiny hitting delayed "skill-shot." Needs to be in perfect position to fight well. Has a wall that is a lot more difficult to use properly than Anivias. No natural "escape mechanisms." Granted his "R" doesn't need to be aimed, but that really shouldn't be the defining factor of Karthus...it's all about the lay waste.

shen

anivia may be a little "difficult" early game, but once she hits 6 she is just: LOL 1 tick of R + E. Easy mode

Ezreal would probably be my top choice for hardest to play.
Actually LANDING your E takes so much more skill than knowing how to wall with Anivia.

Top 3 for me, personally would be something like...
Well.. looking through the champ list almost all of them are pretty easy.
Things like extremely squishy, and covertly squishy (aka seems not squish but is)
Also, things like mixed or confused damage outputs (Characters SIMILAR to mundo, where you have a ranged nuke but are an AD carry but all your damage comes from your AoE on W.)

Confused damage output is what makes a character challenging to me. If I can't figure out what skill I should be using (aka my rotation RQWE, RWEQ, etc) then the champ is a lot harder to me.