In the 1st-gen Insight, Honda put a radius on the aft part of the wheel well. This may have given the air in the fender an easier way out. I've seen it on a few other cars that were styled as being quite aerodynamic.
A lot of the sports-racers from the 70s (e.g., Porsche 917K, Ferrari 512) had the fender cut away aft of the rear wheels. Not sure if it was more for down-force or if it helped drag.
Insight:
917:
The 917 reference might be hard to pull off, but might be cool if you integrate it well.
-soD