I now have empirical evidence that cases that cover the noise cancellation mic on the back of the Droid can cause extremely poor outgoing audio. I just got my wife a Droid for her birthday and one of the things she wanted was a nice case for it. She loved the phone and had no problems with outgoing call quality until the case came and she put it on. Immediately she began to have problems with people not being able to understand or even hear her. We took the back portion of the case off and instantly the phone worked again. Put the cover back on and she became inaudible. So we took a drill and drilled a small hole in the case where it covered the noise cancellation microphone and put the case back on. Problem solved, callers could hear her again and it worked great.
So, if you're having trouble with people not being able to hear or understand you and you have a case on your phone, make sure the case isn't covering the noise cancellation microphone on the upper center rear off the phone (tiny little hole just to the right of the headphone jack).