For me it was Mass Effect.  It was not hard to do, but it sure was time consuming.  What about everyone else?

Beautiful Katamari. 100% collection is a quest of epic proportions that you don't find in many games 
 
also, the online achievements for that game are a bitch simply because its online sucks and you can hardly ever find anyone to play with

I guess Viva Pinata.  Twice.  I don't have many S-ranks to begin with, really.  Fallout 3 on the other hand...

Gears of War. Seriously was 2-3 months of playing multiplayer 3-4 hours a day.

The doritos game. Its the only game I got an S rank in sooo......

I almost got it in AC2, if that counts, but then again...who didn't? 
 
Also, I fucking HATE Mass Effect, so, yeah...

" Gears of War. Seriously was 2-3 months of playing multiplayer 3-4 hours a day. "

" Call of Duty 4. 
 

" @zyn said:

" Call of Duty 4. 
 

What...really!? "

Rock Band 2 or Call of Duty 4.  RB2 because fuck Visions, and CoD4 because fuck Veteran difficulty level, randomly spawning grenades, and infinitely respawning baddies.

Final Fantasy 13, Bionic Commando, Bioshock, Bayonetta, and BlazBlue are probably the one's I'm most proud of. 
 
Rise of the Argonauts and The Force Unleashed were bitches too. 
 
Overall though FFXIII was the one I had the most fun getting the S-rank with. Man I love that game.

Probably Red Faction: Guerrilla since it required me to play through the game twice. I had a lot of fun, though.

I only have 3 S Ranks and all of them are very easy.

My only S ranks are Oblivion and that dumb Doritos game so yeah Oblivion,

Lego Batman :D 
 
 Only have 3 S Ranks, 2 of them is Lego and the third is Uno from XBLA with 200 p.

Track and Field.

 My toughest S-Ranks:
 

• LEGO Star Wars 2, because it's such a grind. 

• Dragon Age: Origins, because you have to play through nearly the full game at least 3 times.

Probably Left 4 Dead or Skate.

Dead Rising for me. 7-Day Survivor is fun, until you realize you can't save at all and have to play for 14 hours without turning the game off. Awesome. Second would go to Call of Duty 2 and 4, because like everyone said, yo. veteran is hard.

Fallout 3. Damn i just got my S-Rank yesterday on it. Damned DLC's and their difficult, long-ass quests! Bobbleheads was also a bit of a bitch.

I've only got all the achievements for two XBLA games so I'll just have to say Shadow Complex. The 50 level one took a lot of grinding to do.

Uncharted 2, and that wasn't particularly hard

According to TrueAchievements it is Pimp My Ride.
I am going to hang my head in shame now.

I'm so close in gears 2 but I'll never reach 100.  But from the 5 I have s ranks in (mw, mw2, dead space, pac-man c.e. and avatar) I'd say avatar for sure.

Final Fantasy XIII, Tales of Vesperia and Killzone 2 for me.  Killzone 2 man...just...wow.

Dead Rising.

I'd say probably Project Gotham Racing 3. Platinum timed laps are insane...  
 
Recently though, probably The Saboteur. It was Grindathon 2010 for those ambient freeplays, but also it was the only way to let my completionist sleep soundly.

My only S-rank is in Fallout 3, so I guess it'll have to be that.

Probably Fallout 3. For the amount of time it cost me.

Probably Hitman: Blood Money. Finishing a mission on Professional, while getting a Silent Assassin rating without any saves is pretty difficult.

I've only 100% Uncharted 1, 2 and Bayonetta. I'd say UC1 was probably the hardest out of the 3.

" Track and Field. "

" The doritos game. Its the only game I got an S rank in sooo...... "

I only have two S ranks; Bully and Oblivion. Judge for yourself, I guess.

Call of duty 4 was pretty harsh.

Being I only did it on 2 games.. Too Human would be mine. I just dont have the drive to get an S rank in many games.

Call of Duty 4 or Call of Duty 2. Veteran was tough in both. Mile High Club in CoD4 wasn't as difficult as it looks.

Call of Duty 2, as far as I can remember,

Well as my only S-rank is in Avatar The Lgend of Aang: The Burning Earth...that i guess. 5 simple achievements near took me 5 minutes.....5 minutes of my life i'll never get back.

Call of Duty 4, Call of Duty 2 and InFamous

Fallout 3

Forza 3 has a achievement to win every single race in the game, theres gotta be like 500 individual races. Not exactly 'hard' but very time comsuming, probably over 60 hours.
I've almost got all the Dragon Age achievements, again, not 'hard' just time consuming.
 
I guess the hardest would be like a game that has MP achievements, like Gears of War 2. I hate the MP, so I'll never get those achievements.

BioShock. 

Rock Band 2 :D. I only wish there were more.

Battlefield 2: Modern Combat. 
 
Anyway, I have too many S-Ranks to count.

Mayhem Intergalactic. It's my only one actually. But getting 100 online victories in a game that never has anyone online is hard. Until I realized that it I could play against bots in online mode and get it that way. ;)