For me, it has to be 1942. I simply naturally suck at the game. I think I spend about 40 hours on the game, and got a score of 414k. I heard Steve Wagner played the game once and got 600k on the game. Of course this was during a time when I didn't use save states, but still, I struggled WAY too much on the game, and only became mediocre for my efforts.
So how about you. What's the game or games you look back on, and go, "Yeah, I spent way too much time on this game, and it got me nowhere score wise."