Could Drew Barrymore have made a good Harley Quinn?
If she of course, wasn't already been used here as one of Two-Face's henchwomen. I say this because Drew Barrymore is one of those celebrities whose whole public persona screams "manic pixie dream girl". Harley Quinn herself, is essentially what you would get if you took the "manic pixie dream girl" trope but made it something dark.
Of course, I don't know if Drew Barrymore could plausibly play a villainous character. The only movie that I'm aware of in which she portrayed what could be considered an out and out villain (besides Batman Forever of course) was Poison Ivy.