There are several champs in LoL which are more difficult to use than others. However, I think anyone can play Syndra or Rumble and do "okay".
But which champion is the hardest to master and consistently do well with?
I think I'll have to go with Orianna. Not only is it important to keep track of the ball and ult at the perfect time, it's crucial to know where to put the ball and who to put it on, as well as using it to engage or escape with W.
I'd say either Poppy or Sion. Even if you survive their horrible laning phase without feeding/possibly getting fed, it's somewhat rare for the team to take advantage of their ults in a teamfight which can easily screw either of them over.