Outside of Batman and the Joker, the character who is most associated with Harley Quinn is Poison Ivy. The two of them have been criminal partners since the days of Batman: The Animated Series, and later portrayals have shown them as being more than just friends (a fact confirmed by
Poison Ivy's powers have been depicted in many different ways throughout the years, so it is difficult to pin down how she would exactly match up in a fight against Harley. Some writers have given her the ability to control nature and create plant monsters (as seen in the Arkham video game series), whilst others have presented her with power over pheromones (like the Purple Man), that allow her to control people (as in Batman and Robin). A mixture of these powers could make for an interesting antagonist.
The big question is whether a romantic relationship between the two would be possible? The issue isn't about former enemies becoming lovers, but the fact that it is two women. Even the Marvel Cinematic Universe, with its numerous films & TV shows, has yet to include an LGBT character in a leading role. Are Warner Bros. really progressive enough to present a relationship between two bisexual women on the big screen that isn't just there for titillation?
If the producers of the film are unwilling to present a romantic relationship between the two, then perhaps establishing them as villains is a way to sidestep the issue without offending anyone.