I think Kate Mulgrew would be a good vocal match for Eris, she has a similar vocal fry to de Lancie’s, and is comparable age-wise. Maybe Bernedette Peters if you want a more witchy-voice to it. But I think Mulgrew would make an interesting casting choice. (Plus, as Janeway she’s dealt with Q enough to make her know how to play to that personality. And since Discord was written as a ponyfied Q, I don’t see why she wouldn’t be able to play that kind of role.)
 
Possibly that chick who plays Missy (formerly the Master) in Doctor Who! She knows how to play crazy chaotic characters who are ancient and yet young at heart. She’d make a great Eris.

@zabchan  
Jane Lynch would be perfect

@Alara Rogers  
alara-sensei, what do you think of my eris, then?

@Conred  
i hear Ursula from the little mermaid

@Alara Rogers  
I would imagine Eris having voice of mrs Krabappel from the Simpsons

@Alara Rogers Funnily enough the only place I’ve seen that is based on history.  
All them movies about Elizabeth I.  
Well, technically the Sinbad animated movie, speaking of Eris, but she didn’t reform so much as ‘not be so much of a dick to wreck the entire city, but she’ll still troll your asses when ol’ Sinbad ain’t looking” at least that was how I took it. Still, it’s an improvement!

@Background Pony #CC9C  
No, if you’ll notice nearly all the artwork (including this piece) ages Eris down so she doesn’t look nearly as old as Discord does. It’s actually much, much more common in fiction (and reality) to see an older man with a younger woman, and vice versa. And if Eris’s relationship with male Fluttershy (I hate the name Butterscotch) was like the one in the show, where there’s a young gentle friendly guy trying to teach an insensitive, selfish jester of an old woman that she can actually have a friend… it would be a setup I have never seen in fiction (whereas young woman teaches old man about friendship is not a terribly uncommon plot.)
 
Of course I’m not sure how you could make Eris look Discord’s age. It’s the bushy eyebrows and beard that give Discord the appearance of age – the white hair just looks like a hair color, with all the wacky colors in the ponyverse. Discord is immortal, so he’s not exactly going to get wrinkly. Eris doesn’t get a beard (most of the time, and it’d be hard to recognize her as not Discord if she did), so I don’t really know how you’d draw her to look as old as Discord does. Maybe you’d just have to do it with having a voice actress who’s de Lancie’s age.

I think even more people would ship it if Fluttershy was a guy from the start while Discord was female. They somehow reject the idea of young mare being with an ancient chaos spirit with mature voice but would probably ship a younger stallion(voiced by Elijah Wood)with mature chick with voice of an older woman like Madonna for example.