For me it was Civilization. I bought one of the earlier iterations and simply Could Not Get Into It. For many gamers, it's like the greatest PC game ever, and it just never clicked with me.
Half-Life 2 perhaps as well. I loved Half-Life to death in spite of my legendary
first person and sometimes third person shooter motion sickness problems. With HL2, I bought it op
ening week for something like $64.99 at an EB store, and promptly got lost in the train cars scenario. For whatever reason, it didn't click with me even if the masses and critics found it Best Shooter of All Time.
If you want to get really creaky, some legendary games like System Shock (the first; loved the 2nd); and Ultima Underworld were games I bought in my early PC gaming days that didn't click with me either.
This whole thread illustrates the folly of Metacritic. Lots of my favorite games are something like 33, 44, 56 whatever on Metacritic. If you totally let other gamers and critics decide what you should play, you'll never know what you miss out on.