Be inventive, you really can't avoid serial numbers, but don't stop there - you could generate a number, hide it somewhere on the hard drive, and work out an authorisation number from that and the username, which you would provide the key for.
A reinstall would possibly mean a new serial, but that's all that would be affected. It won't stop people cracking and distributing, but really that's a whole other threat you should consider seperately for now.
You would have to do some investigating periodically to find published serials or cracks, and possibly you'd have to threaten webmasters into removing cracks and downloads, all that while updating the software to ween out the cracks. Like you'd break a crack each time you released an update, whether it's a simple serial ignore or something more drastic, it seems to be the preferred method by internet software firms.
Van-B
Put those fiery biscuits away!