I installed Thunderbird portable while plugged into my Vista machine and created 4 IMAP accounts. Everything was working fine.
When I plugged my drive into my XP laptop it still shows account entries for the 4 accounts, but none of the folders, and can't seem to connect to download again. I put it back in the Vista machine and everything works perfectly (it re-learns the folder structure from the accounts and gets new mail).
The only difference I can note is that the drive letter changes between machines, but the pref.js seems to update the drive letters just fine. In the Thunderbird options pages, it reads the proper drive letter also. I can't find any "accidental" files on the Vista machine that show it was storing something locally.