I have a horrible time with this! I switched from a BB Tour to the droid, and it really is a night and day difference. But in the 3 months I've been running with this droid the only complaint I have is call quality, it's terrible! Though it does not happen (that I know of anyway) on every call but my girl was always quick to just hang up with a "well I couldn't understand you" even my parents have a hard time hearing me. I got my girl a droid as well and she's had the issue a few times as well. To be honest I don't mind mainly because it's a great way to get people like me sisters off the phone in a hurry
but it does become a pain when I have to call from a landline because no body on the conference call is able to hear me during my weekly meetings. I use to be able to do those on the run, not so much anymore lol. Overall if it happens I just talk really loud like the nokia guy in the art gallery, every phone has it's quirks and to be honest I would still take my droid hands down every time over my old tour
But this is just one dudes humble opinion
_EDIT_
Guess I should note I tried with and with out a case also (like the iphone) tried holding it differently. Also tried to look around the settings but nothing seemed work