It's always a combination of things that ruin or make a game. You can have the best combat system ever devised, but if the art design is mobile-tier, the quests are all the fetch variety, the writing raises your grandmother's corpse only to shit in its mouth, and the engine has a worse smell, it would still be unplayable.
It would also depend on what you mean by kill. If you mean its popularity, we see how Bethesda, Bioware and Blizzard are murdering their franchises - complete apathy and lack of self-awareness. Sometimes focusing on graphics to the detriment of everything else, sometimes having no plan at all (due to apathy and indecisiveness), sometimes just plain bad luck.
As for killing a game for the Codex, that's a more difficult question. I'd say the first big thing is mangling the start of the game (PoEs), it's usually the writers who are most at fault, followed by the level designers. If the start is playable, then it's the writing in the sense of when it's TOO bad (PoEs, D:OSes, Wasteland 2, Numanuma, etc.). When that is okayish, it's the combat system, I'd say the biggest hurdle is if it's too repetitive and mindless, which a lot of recent RPGs have fallen into. If THAT is also okayish, I guess it's art direction, there's nothing worse than low budget 3D Unity-looking game. Everything else can be overlooked I guess.