I've recently been having a problem where MC doesn't recognize that it's already synced to my iPod, and insists it needs to delete and recopy everything. Here's the chain of events:
1) Start with a fresh iPod (5G 30GB)
2) Make sure current FW is loaded via iTunes
3) Initialize in MC
4) Sync in MC
5) Use the iPod - combination of standalone, and with the harman/kardon drive+play system in my car
6a) Sometimes, I come back and it syncs fine.
6b) Sometimes, I plug in, and it'll tell me that all of the files currently on the iPod (~3000) need to be deleted (if I have "delete files not in sync list" checked) or that the iPod will be over capacity (if unchecked)
7) I can go over to iTunes and interact with the iPod just fine, so the iTunesDB should be good (or else MC's filehandling isn't robust enough.
The workaround is just to initialize it again and reload, but I don't think that's acceptable at all - if I have to wait 40 minutes to re-sync my music, it's not worth it to use MC. Next time it happens, I can provide an iTunesDB file if that'd be helpful.