In terms of difficulty I would say King Aurthur: The Role Playing Game. You really need to becareful how you play the game. You cannot make a mistake...even on normal difficulty...heck, botching one battle on easy can make you have to reload and if you go to fast though the main storay line you will end up fighing things way too tough.
A Baldur's Gate no quick save chalenge is pretty darn tough too, but then so would any similar chalenge.
In terms of controls and interacting with the game...I would say a flash game called Happy Wheels. Warning...before you google that be warned it is not for the faint of heart. (some maps are easy, but others are practically impossible.)
Edited by Vagrant Storm - 8/15/11 at 9:19am