In A Return to Harmony, for the vast majority of the time that the rest of the Mane 6 are greyish, Twilight seems to not notice and think they've just had a change of heart somehow. This being in the face of them more or less having complete personality flips and quite obviously losing a majority of their color. Is it an oversight by the writers or was Twilight actually aware and just not sure what to do?
Despite being one of the worst of the new series (in my opinion), I don't think this was a production issue. I think the visual clue was more of a hint for the viewer and wasn't meant to be as obvious to Twilight.
The personality flips on the other hand should have been spotted. Twilight isn't the most social pony however, and may have missed it under the extreme pressure of trying to save the world. In fact, had she noticed, she may have assumed it wasn't a change but merely a response of her fellow ponies to the stress of the situation.