I would have to say Monkey Island 2: LeChuck's Revenge in "Hard Mode". I had an easier time with LEisure Suit Larry - and it was all about this one little tiny part....of course, this was when I was 10 back in 1993.

SPOILER ALERT!!!
...There's a part where you are playing a spin-the-wheel game with some Cierano looking dude in the alleyway. To get the winning number/color combo to win the prizes you have to go to another alley down the dock from him, and knock on a door where some big hand holds up strange finger combinations and says stuff like "(holds up 5 fingers) if this one is two, then (holds up 2 fingers) how many fingers is this" - and if you get it right, he'll tell you the number and color that will win.

I swear, for a month straight I Could not, for the life of me, figure it out. I asked my buddy PJ at school - his idea did not work (some complex mathmatics thing). I called the LuscaFilm hotline (1-800-something-Jedi) and got little to no help there. I basically bluffed my whole way through it eventually beating it after 2 months of random tries guessing the right number....

Skip ahead about 10-15 years, I look it up on the internet and literally facepalmed when I discovered he's just expecting the previous number of fingers he held up, 🤣.