Who has the most to fear on ABC's Once Upon a Time now that the Evil Queen (Lana Parrilla) is on the loose?

Now that the Evil Queen has separated from Regina, there's no telling what havoc she might wreak.

Once Upon a Time co-creators Edward Kitsis and Adam Horowitz spoke recently about the Evil Queen splitting from Regina and what might ramifications there are to come.

"In the pilot episode of the series, she warned, 'Enjoy this happy day - she's going to rip everyone's happy endings away.' I think she looks at Regina as someone who failed to do that," Kitsis told The Hollywood Reporter. "Who is in trouble? The entire family because she has her sights not just set on Regina and Snow [Ginnifer Goodwin], but also Emma [Jennifer Morrison]."

The Evil Queen will be the most imposing villain Once Upon a Time has seen in a long time, according to the creators.

"The Evil Queen, in this new form, is quickly shown to be formidable in a way that we haven't seen any villain in a long time, if at all," Horowitz said. "How to defeat her, if she can be defeated, is a very big part of the storytelling. Obviously, we don't want to say what that is, but that's something that our characters come face-to-face with quickly."

Though we've seen plenty of soul-searching for Regina, we have yet to see much of anything in that regard for the Evil Queen. The creators are hoping to explore this in the season to come.

"Thematically, we want the Evil Queen to really look inside herself," Kitsis explained. "We've seen her be redeemed, we've seen her realize that she can't just resort to the Evil Queen to get what she wants. This year, we really want to get in her head and wonder: Can you separate the darkness, or is that a part of you?"

Once Upon a Time season 6 premieres Sunday, Sept. 25 at 8 p.m. ET/PT on ABC.