I'd like to see wine produce real PE dll files that use unix system calls as a back end. For example, a real kernel32.dll in PE format that maps at the same addresses as the windows XP version, and so on.
PE executables could be seamlessly loaded with an ibcs extension and properly linked against wine's real PE system dlls.
Adapting wine to that sort of architecture would make it as native as real windows, and the bulk of wine's sources wouldn't need to be edited.