Michael Hanscom notes that Pixar has not made a movie with a lead female character and this unfortunate trend looks to continue with Wall-E.
What's been frustrating so far is simply that in many of Pixar's prior films, there's no particular reason why one or another of their characters couldn't be female rather than male -- would Ratatouille have been any less well done if he were a she? Would the rescue of the ant colony be less spectacular if Julia Louis-Dreyfus had voiced Flik against Dave Foley's Prince Atta?