A game can have some warts and still be top 100. These things are ultimately judged by the unique things they do best, not what they do poorly. Of course they can't have serious flaws such as Arcanum.
That said I have some general issues:
a) Single-player RTS games. RTS's are simple games at heart and no single RTS offers enough variety of gameplay to be considered truly great. I get why Homeworld has fans but it clearly illustrates this problem. These things can only be judged by their depth in 1v1 multiplayer, basically the video game version of Chess, which is why out of this genre I selected Red Alert. StarCraft otoh is just too twitchy and not cerebral compared to Red Alert.
b) FPS games. I could never get into these for one reason - I just find it ridiculous to play these games with a mouse or gamepad. Get a light gun for chrissakes
c) Games that are too cartoony. I'm not a little boy anymore. Super Mario World and SMB3 might seem brilliant when you were 12 or 19, but it's hard to take a game where you stomp on koopas and goombas seriously once you are 39.
Specific games:
Tetris: Ultimately the strategy to Tetris is limited. Then it becomes just a distraction/ time-waster.
Street Fighter 2/ Championship Edition: It's true that it inspired an entire genre and deserves credit for that. But in the 20+ years since it has been far surpassed by its successors. Let's not get too nostalgic here.
Nethack/ Rogue: Ultimately I went with the most refined version of this genre that I feel in many ways transcend the genre, which was Invisible Inc.
Gain Ground: I saw Gain Ground in HCG's top 100, and it would probably make my top 100 too, but not my top 25 since I think again, a lot of what makes Gain Ground special can also be found in Invisible Inc.
Castlevania/ Castlevania 3/ Castlevania: Bloodlines/ Meteroidvanias: I love Castlevania but ultimately 2D platformers really do not really fit horror or exploration that well. The best fit for 2D platformer I feel is Ninja platformer, which is why I went with the masterpiece of the 2D Ninja platformer, Shinobi 3. And if not one of the Shinobi games (all are really amazing), then Strider.
Ikaruga: This has the reputation for being the "ultimate" shooter but honestly it's a) too short and b) too abstract. For me the two gems in this genre are Boogie Wings and Steel Empire.
Gauntlet: Gauntlet is in my top 100 but for top 25 I went with Diablo instead. Gauntlet was a great multiplayer game, a game that captured the imagination of a generation of gamers, and a formula whose legacy includes everything from Diablo 3 to Assassin's Creed to Gain Ground to Rogue/Invisible Inc to Grand Theft Auto. But really, like Tetris, it's a game whose strategic depth is has a limit.
Europa Universalis/ Crusader Kings 2: Ultimately grand strategy games are using the formula invented by KOEI, and while Paradox's efforts are interesting and baroque, they are ulltimately not as fun. So for me, Uncharted Waters still holds the throne uncontested.
Civilization 2/ Civilization 4: Ultimately the weakness of this series is twofold: one, they are pretty terrible multiplayer, and two, they are strategically repetitive. The terrible multiplayer is worsened by poor AI, and the strategic shallowness is worsened by endgame complexity bloat, which this series has never managed to solve. Only SMAC ended up transcending these limitations. The enormous creative and strategic depth in SMAC's tech tree means that even after thousands of hours, one can still find a new challenge to explore and overcome in this classic.
