I mostly mean with games, but I guess this could apply to movies or books or other things.

I've mostly had this problem with gaming. One major one for me was Civilization IV. I was reading about the game for a while, thought it sounded awesome, read all the amazing reviews, bought it, and just could not get into it. I don't know why, I just got the desire to play something else everytime I sat down to play it. I read the manual, did the extensive tutorial, but I just never stuck with it. I've returned to it a few times over the years with similar results. I still don't get it, on paper it sounds great: run your own mini-civilization, with a lot to manage. Sounds sweet, but for some reason I can't get into it. I still kind of have the desire to like it. I will probably re-install this year and give it another go .

Alpha Centauri. It's an amazing game, but it just can't seem to keep my attention. I think it has something to do with the pacing of it.

edit: If there is a game that needs a sequel, it's that one.

That's happened to me before too. I see something really cool and want to do it, but there's always something else. It might just not be your kind of game.

Red Dead Redemption, Skyrim and Morrowind.

I heard Morrowind was supposed to be the amazing RPG and I spent 40 hours in the game, apart from like 10 minutes when I played around with levitation I had no fun what so ever in it, I tried to hard to like the game and to overcome it's horrible design choices but in the end I just said to myself "It ain't worth playing this game if it has to take 40+ hours for it to start getting enjoyable."

With Skyrim I first enjoyed it for like 60 hours or so then it started to go downhill slowly.
After my 2nd playthrough I swore off the game and went about my business.
Then after the game had been out longer I got some mods to fix the things that I didn't like but I still could not get into it.
I tried so hard to make the game enjoyable by using mods to fix the glaring issues I had with it but there are some things you simply cannot fix with mods.
So I played for maybe 20 hours on that 3rd character, forcing myself to try and smile and enjoy things but all I could feel was emptiness inside of me.

As to Red Dead Redemption, I liked the first part of the storyline, after that it just went downhill, but I thought to myself that "I might as well continue on as it might get better later".
And it did, in the third act, and that was the shortest one, then the anticlimactic ending came and I felt like it was a huge waste of time.
During the later part of the first act and the whole second act I forced myself to play it cause I was hoping it would get back to it's quality in storyline.

I wanted to like all three of these, I tried to make myself like them, but I ended up resenting them even more for wasting my time on them.

http://morrowind.nexusmods.com/mods/23746

I refuse to use mods on my first playthrough, and it's not just the dice rolls with attacks that is horrible, it's everything.
You can't fix everything with mods.