I have this problem sometimes with my dual-screen setup, especially when I'm juggling lots of things around.
Occasionally I seem to be able to move a window entirely off-screen (I'm not quite sure how) and I can't get it back. If I do a 'hide all' in the application's menu (usually it's Mail.app, so let's stick to that one for the example), everything disappears and Mail seems to think it's got an 'inbox' window in the Windows menu, but there's nothing visible. Closing and restarting the app doesn't seem to help (as the app is helpfully remembering where my window previously was) and all I end up doing is shutting down the Mac, unplugging the second monitor and restarting it, opening the application again and this seems to persuade the Mac to rethink the main window position, and all is well. I can then restart the second monitor, etc.
Is there a better way? Is there some way of marshalling windows back to a specific monitor, or a utility for moving 'open'/running windows? Am I actually doing something wrong? :-)
I'm not using Spaces, by the way - so I'm pretty sure this isn't some weird Spaces issue. :-)