I have takedown mapped to the middle mouse button. When I first started the game this worked fine, and takedown worked every time I hit the button. Now I have a problem where takedown randomly fails. I hear the noise, hit the button and nothing happens except I then hear the noise again. Then I have to hit it again or spam it to get it to work, and often the guy gets alerted rather than taken down. It is as if the game can't decide to melee the guard or use takedown. The button still works for melee otherwise. I am not sure when this started but it may have been after I learned the "jungle run" skill that lets you move fast while crouched.
Edit: Since posting this I noticed that the melee ability also fails if I hit the melee button at the same time that I release the "forward" key which I have mapped to "D" rather than w. If I wait a split second after releasing the forward key it will still work. Apparently the brief stopping animation that occurs after releasing the forward key makes the melee button fail and presumably takedown as well. I can reproduce this effect consistently.
I should note I am using the steam version of the game.