Could you elaborate? (In particular, could you please describe the game's save system?)

You misspelled shaving.

Usually a combination of issues that make me give up on a game, bit I seem way less patient these days. Ones from recent memory would be...
Remember Me's boring combat mechanics and being lead by the nose style
Alien: Isolation's lack of focus and direction with when and how to deal with or avoid threats
Dead Space's clunky controls (and not just in the sense they wanted them to be clunky), and idiotic 'puzzles'.

For me, it's the random names in Rogue Legacy. After hours of grinding I finally defeated the first boss, such a great achievement for me at that time(because I lacked the practice playing action platformers), with a character named Sir Useless. My second great achievement in that game was defeating the second and third bosses in the same run with a Paladin named Lady Chun-Li. In a game where the main character was already utterly disposable, diminishing even the memorable moments with retarded names, completely ruined the game for me. I'm sorry I couldn't enjoy the game, especially since so many people praise it immensely.

Also, locking the last class of the game (the traitor) behind the most difficult 5 battles of the game, thus preventing me from 100% completing the game, might not have been the most brilliant game design idea. I played the game for 27 hours, before I gave up, realizing how much effort and practice would be required to finish those last 5 bosses.

That's exactly how I saw it too, plus I played him as a buffing/AOE hero so it didn't bother me at all. But I can see how it would be deal breaking if you wanted to play him as a heavy/light warrior.

This thread is a good collection of general things that ruin video games. These things can come single or in bunches but as long as the competition is strong one can afford to be picky.

Diamond Dan and the Towers of Treasure

is a very nice puzzler. I bought it long time ago DRM-free from Direct2Drive. In the meantime Direct2Drive drive closed and was relaunched. But when it relaunched some games were missing. Diamond Dan too. They promised to bring the missing games back after some time and they did. But now the game is infested by SecuRom DRM. This ruined the game for me.

<span class="bold">Indigo Prophecy</span>   (aka Fahrenheit)

In one word : <span class="bold">two color sequences</span> simultaneously, in a relatively short time.  You focus so much on them that you have trouble following the overall action.  I'm not against quick-time events if they're used in moderation.  I don't have any problem with Telltale's adventure games, but Indigo Prophecy miserably fails in that department.

Legend of Grimrock - timed puzzles

Alan Wake - the atrocious control system and messed up camera on the PC. It is basically unplayable with mouse and keyboard. And no, I'm not going to get a gamepad for just one game.

and yes, I agree, Fahrenheit is ruined by QTEs

Theme Hospital and its stupid janitors unable to clean the ground quickly + the pandemic situations when you have to cure the patients with a nurse unable to find them = Hospital closed !

Rage quit !

Sacrifice
Terrible performance, some of the missions were unplayable cos of the bad framerates. Shame cos there was a lot of great things about the game and I really wanted to like it. I'm going to give it one more chance though

Arma Gold
Terrible performance made playing this game a nightmare. I never finished the Queen's Gambit campaign cos in the last mission, the framerates dropped to unplayable levels

Turok 2 (N64 Version)
Savepoints were too far apart

Rebel Assault
The worst controls I have ever seen in any game since I first started gaming

Crimsonland
While I still enjoy the game, if a shitty weapon spawned, you were going to be starting over

The 11th Hour
That annoying host!!!!! STFU ALREADY!!!

Heroes of Might and Magic 5
The aesthetics made the game look more like WOW than HOMM. I'm still going to give this one a second chance too

Age of Wonders 1 & 2

The heroes become ridiculously powerful halfway or so into the campaign, to the extent that armies become almost useless. You could opt to play without your hero though, but then you would still have to contend with the likewise powerful enemy hero. If only they balanced hero powers a bit differently, so that there was a kind of ceiling to their power more or less equal to two top tier units. Then the game would be pretty much perfect.
Still it doesn't totally ruin the game because it should be feasible to just keep your hero at your starting city, and perhaps just bring him/her along to deal with the enemy hero, who usually just turtles in one city.
I also struggle to get past the aesthetics of the game. But I'll perhaps also try it again someday. The thing that chased me away initially was the horrendously slow start to the game. Perhaps if I persist and reach a point where it becomes really challenging I'll forget about the graphics, like with HoMM 3. Though come to think of it, apart from the world map, HoMM 3 has got beautiful graphics.

Quake Live
"Hey, let's turn this free-to-play game on both web browser and Steam into an Steam exclusive....huh? Add a free edition and a pay-once-get-all-stuff thing if people like it? What are you, retarded? Let's may it pay once to play only! For 10$!"

and that's how Quake Live died.

Zelda Skyward Sword : EVERYthing motion controlled (by only one aspect, this... and then, a boring, empty sky & a little too much backtracking, gathering this and that to open access here and there...)

Zelda on Ds : touchscreen only... really, no d-pad and buttons option. I could not play them.