Windows sysprep, I believe the answer is Yes.
'Prepare Computer for Imaging' task, no; it takes care of the GUID.
The GUID you need to manually delete--without letting the Agent check in with the server again and get a new one--is HKEY_LOCAL_MACHINE\SOFTWARE\Altiris\Altiris Agent\MachineGuid value.
A better policy if you don't want to use the built-in Task (Prepare Computer for Image) is to install the agent, but to not let it communicate with the Notification Server. You know you've done this correctly if there is no MachineGuid value in the registry.