Today, all of a sudden, when I opened it, the main viewer window would not appear. The program seemed to work fine in the background: I received notification of new emails, the unread count on the icon would get updated, but there was no window. Trying to use Exposé, "Bring all to Front", "Arrange all to front" wouldn't bring any improvement. Right-clicking on the icon and selecting "Show all windows" would show transparent squares with actual window titles, but trying to click on them would make no difference. File -> New Viewer Window seemed to produce new "transparent" windows, so the list under the Window menu would get longer but I still wouldn't see anything. Using Applescript to resize and reposition a window gave very strange results, with the window appearing half-broken (no Preview column, no Mailbox list, missing toolbars etc) and eventually disappearing again.
Out of desperation, I quit Mail and started digging in the filesystem. I eventually managed to fix the problem by doing the following:
# 'tar' is just for safety, delete the gz file if fix works
tar -czvf ~/Desktop/Preferences.tar.gz Preferences
rm -rf Preferences
When I then launched Mail, the Viewer window finally appeared and worked correctly. It had lost my original layout, so I had to set a couple of preferences again, but apart from that it seemed to work well and it didn't lose any mail or account information.