Use online update to block those unlicensed copies.
Verify serial number from different modules of your application and do not use a single function call to do the verification (so that crackers cannot bypass the verification easily).
Not only check serial number at startup, do the verification while saving data, do it every Friday evening, do it when user is idle ...
Verify application file check sum, store your security check sum in different places.
Don't go too far on these kind of tricks, make sure your application never crash/get into malfunction while verifying registration code.
Build a useful app for users is
much more important than make a
unbreakable binary for crackers.