If you manually delete iSync 2.0 (which comes with Mac OS X 10.4 Tiger) and then install the iSync 2.1 update, the application won't open. Its icon will become blank (a generic icon) when you click it.
To resolve this issue, perform an Archive and Install installation of Mac OS X 10.4 or later, then install iSync 2.1. If you want to preserve your existing user accounts, Home folders, and network settings, be sure that you select the "Preserve Users and Network Settings" option (this is selected by default).
For the best results, use Software Update after reinstalling the operating system and before launching iSync or any other applications.