I don't mean like you just let it fall away over time or something. Have you been going for an S-Rank on a game and then just decided you couldn't do it?
 
I just started playing Darksiders for the first time and decided to fire up my first game on the hardest difficulty. For some games, like Call of Duty (back in the day on the PC at least, I haven't kept up), I could play on the hardest mode and it just meant slow going, but I could do it. I found Apocalyptic on Darksiders to be no fun, though, and I've decided to step back down to normal. I know that I won't play through it again. No S-Rank for me!

Geometry Wars Retro Evolved and Streets of Rage 2 are the most recent I've come to terms with.

Gears of War 2. Multiplayer is too frustrating to even get to level 40, I'm currently 38, much less reaching 100.

Well I share my Live account with my brother and he relishes in really difficult challenges so even if I give up he'll almost always get at least an A on a game. Most of the games I have an A or S on he played, and most I have a D or F on I played. I just don't have the patience to play games on super hard difficulty settings or do ridiculous challenges. I'm playing Assassin's Creed 2 now and there's no way I'm collecting 100 feathers. That would just take too long and get too boring too quickly. I guess I'm just not that competitive.

I always set out to get an S-rank in a game if i've been excited for it. Like i'm totally set on getting S-Rank in red dead redemption when that comes out because it looks really really good and i won't get bored of playing it. Realistically though, i only got 300/1000 in GTA4 and that's made by the same people so i guess they'll be of the same annoying grain. 

I gave up on S-ranking Fifa 10 because there is an achievement for getting 100 Ranked wins i was going for.. i got to 100 after a lot of work  only to find out disconnections by the other guys don't count, and they made up about 60% of my wins.

Gears 2 - have everything but rank 100 (on 67)...justnot going to happen although I will continue to play it regularly
Batman AA - I don't know, I just stopped playing it for a few months and I just don''t feel like playing it again
Silent Hill homecoming - I was getting all the collectables using a guide but I havent played it for so long that I doubt I know where I'm going
GTA4 - damn multiplayer cheevos

" Geometry Wars Retro Evolved and Streets of Rage 2 are the most recent I've come to terms with. "

Left 4 Dead, and most recently Final Fantasy 13.
 
If you want all 1,000 in FF13 you better have a shit load of time on your hands. It's not that it's difficult, just brutally time consuming.

Just about every game that doesn't let you play through certain levels whenever you feel like it. I got 1000/1000 in 2 games, both LEGO games that makes it a lot easier. I play games because they are fun, not because I need useless points. 

(Vanilla) Street Fighter 4.  Did not expect those challenges to be so hard/time consuming.

Lost Odyssey before the dlc had an achievement called Treasure Trove where you had to get every single piece of shiny/hidden treasure in the world.  I went around for hours being stuck on 980/1000 before i just said F that.  I generally have fun collecting achievements, but any game that has a play this for X amount of hours(or get 903423423 kills) or beat the game in under X amount of hours generally make me sigh.  I hate rushing through games and generally don't like doing multiple playthroughs unless I enjoy the game.  I also don't want to spend 100 hours on a game I don't particularly enjoy playing online just to get the time achievement or the 9 billion kill achievement.

I hate rushing through games and generally don't like doing multiple playthroughs unless I enjoy the game.

Bayonetta: Normal was hard. Insane? Forget it. 
 
Forza Motorsport 2: 1 Million Online winnings? Is that even possible anymore?

Sonic Unleashed. Motherfucker, what a tedious game.

Audiosurf and most of the games I've rented.
I really see no reason to go through Rise of the Argonauts a 3rd time.

I'd love an S on everything (I'm like Vinny with my ticking all the boxes and removing all the icons from my map - I did 1300+ twiddle actions in The Saboteur for crying out loud).  But (and these are only the ones I thought, when I started out, I had a shot at - I know I'll never be able to - or have the patience to - do some of the hard ass stuff in Rock Band, Forza, Hexic, etc.):
 
Batman AA - Whoever says Brad is a sucky player is an idiot. Those combat challenges are a pain (particularly Shock and Awe). I thought, yeah I'm getting the hang of this and then a couple of days later I realized I'd hit a wall with my skill level and put the controller down.
BioShock 2 - I'm not big on multiplayer but I enjoyed B2 for a while. However, once I hit level 20 I thought: Naaaah, I've had my fun (and with the new add on including Achievements, well, forget it).
Braid - Maybe I'll try a timed run again sometime, but probably not.
Puzzle Quest - But only because no one is playing it online anymore (anybody wanna help a brother out here?)
PoP Classic - I'm way past the time when I could play an old school hard core one life platformer.
Mirror's Edge - Ow. I cannot do the wall climb, 270 degree turn thing that you have to do to get 3 stars on The Office (well, I can't get a bunch of the other challenges either).
Tomb Raider: Legend - No, I am not paying $30 for 250 points, thank you (I paid $20 for 1000 points buying the full version of Anniversay).

I have given up to platinium GoW 2 (the collection obviusly) 1 trophy away from  plat, i just cant be bothered doing the challenge of the titans, it just sucks i cant get my plat because of it

Borderlands, Screw You mad Moxxi And your Underdome!

Yeah, most of them. Especially games with collectibles and random shit to do. The Saboteur is a motherfucker in that regard; I got 750 points in one playthrough, but to get the S-rank you have to do like a thousand ambient freeplay events. No thanks. Same reason why I couldn't be bothered with the feathers in Assassin's Creed 2 (fuck you mama) and the artifacts in Darksiders.
 
I'm not usually a fan of using guides in games, especially when it comes to achievements, and I never S-rank any game with multiplayer achievements because I hate multiplayer. Because of that, I only have three S-ranks. 'Tis the price I pay.

I don't really go for S-ranks, but the most recent game that I gave up playing was killzone 2, stopped playing at Radec's balcony on elite, before the patches.

Actually probably none, because I never play a game and think I'm going to S rank it.  The  only time I get an S rank it's because I'll have played the game for a while, and then notice that I only need a couple more achievements that aren't to difficult or time consuming, so I go for it.

Bioshock I guess. Only have the Brass Balls achievement left, but I don't feel like investing any more time into that.

Braid. Was following a Youtube speedrun to try and get through in under 45 minutes but I think I missed out by a minute or two because of some stupid mistakes. Not trying that again; that game wasn't designed for speedrunning in the first place.

" I don't mean like you just let it fall away over time or something. Have you been going for an S-Rank on a game and then just decided you couldn't do it?
 
I just started playing Darksiders for the first time and decided to fire up my first game on the hardest difficulty. For some games, like Call of Duty (back in the day on the PC at least, I haven't kept up), I could play on the hardest mode and it just meant slow going, but I could do it. I found Apocalyptic on Darksiders to be no fun, though, and I've decided to step back down to normal. I know that I won't play through it again. No S-Rank for me! "

Any game with more than two or three multiplayer achievements. I'm just not into online multiplayer.

Read Dead Redemption. I was going strong. Got the 100% achievement, but I can't see myself getting to max level in multiplayer.  
 
The main reason I gave up is that the multiplayer is or was jacked. I don't know if they fixed or not yet. Anyway, I couldn't get into games and when I did it would just disconnect me to the infinite loading screen after playing ten minutes.  
 
Maybe if the multiplayer connection issue is addressed I will give it another shot.

Call of Duty 4 fuck  that game.