kennens star

I find Tibbers is pretty hard to land.

Pantheon's Q.

If Annivia's wall counts, that definitely takes the cake. Nidalee has it harder over Blitz though, given that in order to make it the most effective, she has to hit from the maximum distance, thus giving the opponent a chance to run out of range/sidestep (a good Nidalee should almost never throw a Javelin such that they can run out of it's range, but it's all too easy to sidestep that molasses-slow missile while running).

Edit: With regards to Ashe and Trueshot Barrage: Certainly, they may be more effective that other skill shots if landed correctly, but I feel they can't possibly be harder to land than other skillshots based solely on the fact that they both target only heroes.

Ashe's arrow. If you manage to land it perfectly from across the map, kudos.

Landing Anivia's wall so it stuns.

I'd agree that Anivia's wall is the hardest skillshot to place effectively, but I'm actually surprised Malzahar's call of the void hasn't been mentioned here, either... half the time when you successfully land a hit, the damage that you deal will only be half of the full value.

Aiming an alistar headbutt i think can be up there.