I've wondered about this myself from time to time.
Assuming SEP is following Windows' "Specal Folders" locations, if you were to build a new Windows installation by using the "FolderLocations" settings in an unattend file, SEP's content should follow the %ALLUSERSPROFILE% to the alternative drive.
http://support.microsoft.com/kb/949977
Alternatively, you could also try using the Windows junction function so you could move the defs to another drive, but make Windows (and SEP) think its still in its original location.
I must stress, I've not tried these myself, and I doubt the junction one would be supported by Symantec, but it might be worth a try if you're stuck and need something quick