Been playing Anivia over a year now and I still occasionally mess up a wall and miss her Q more than I want to admit. Getting good with her pays off though, she is probably the most scary mid lane champion in league.

Cassiopeia is also very difficult to play effectively, but is also a very scary mid lane if played correctly.

Vayne is one of the harder adcs to play, she isn't just a right click to win. She has a strategy to her and has a high payoff for effective play.

Brand can be very difficult to use at his full potential, you have to constantly look for opportunities to light everyone up to make the best use of his skills.

Ashe is also difficult to play efficiently. Arguably one of the most useful adcs though.

1. Darius
2. Sona
3. Garen
4. Malphite
5. Warwick

Duh.

These are my experiences with mid playing and champions i have used. I do not own more than 25 champs but from my experiences, these are what I found to be hard for me but worth while if mastered.

Cassiopeia- She can be difficult to learn but if you can master her, gg for mid lane
Viktor- He's kinda hard to play, if you get his combo down he can kill people that have full health!!
Shyvana- She may see like trash but she has so much cc,(stun, slow) also her ulti is soo crazy
Xerath- He is like an artillery tank, problem is you need to know where to place him(positioning)
Morgana- She is kinda easy to learn but mastering her isnt that easy. She is soo good if you know how to use her.

Definately superman. Hardest champ to play by far. Batman too. God those guys are impossible to play as.

Orianna
Cassiopeia
Twisted Fate
Syndra
LeBlanc

I didn't pick these champions because they're hard to play, I picked them because you can tell the difference between a good player and a great player. A good player will go around, do some damage, get some kills, be part of the team. A great player will crush their enemies, see them driven before them, and hear the lamentations of the women.

Honorable mentions:
Twitch
Shaco

Heimerdinger should be definitly in top 5 because he need EPIC positionning and good lane phase otherwise he is trash. Also, start way behind any of the common "Hardest" champion (cass, syndra etc...) because... well he is heimer... Furthermore, his e does not only require to hit, he really need to hit exactly the champion ±1% which is why he is definitly my #1 hardest hero

other one in no particuliar order :
-cassiopeia
-syndra
-draven
-karma

Tryndamere
Darius
Warwick
Master Yi
Diana

Shaco is pretty hard to play

anivia
shaco
orianna
twisted fate
rumble