the most clever ones (not hardest) that comes to mind now are
Discworld Noir -
Spoiler:The upside down Azile... i remember how much I wandered before even getting the idea that you can use your clues as items....
DOTT -
Spoiler:haven't played it for a long time but I do remember that there were at least several very clever puzzles involving the time shifting... like the transformation of the USA flag which turns into a tentacle costume, or the hamster and the huge amount of coins....
Curse of Monkey Island -
Spoiler:when you had to inhale from a helium balloon and then make a helium bubble with the gold tooth. love when the mouth/hand/eye is not just talk to/use/look
Sam n Max Hit The Road -
Spoiler:the inside out cat. it's not actually a puzzle but...