I’ve been trying to figure this one out. It obviously can’t be any of the leads. Nor is it any of the fan-favourite secondary or background ponies, since he’s drawn all of them (Derpy, Lyra, Tavi, Scratch). Even lesser background ponies like the Flower Triplets have appeared in his comics, I think.
I am reminded of one particular fan who has a pathological hatred of Daisy, to the point that every time she appears, he says “I hate you, Daisy.“
So then, who’s missing? Well, I’m pretty sure Cadance & Shining Armor haven’t appeared yet, but I doubt he’s allowed to reject either of them. Could be Twist, since the meme is that she’s Worst Pony, and I don’t think Andy’s drawn her. A lot of people hate Flash Sentry (Brad), but Andy said he kinda liked the movie, and from what I understand, Flash isn’t offensive enough to warrant that level of hate, though I could still see Andy rejecting him on no-romance grounds.
In short, it’s probably either Twist, King Sombra, Flash Sentry, or The Twilicorn (and yes, I do consider her a separate character, until such point that the show convinces me I no longer need to)