OS: Windows 7 64-bit
ZC Version: 2.50
I first discovered this with the Goto Location cheat, but this can be triggered by any drop-down menu. You don't even have to be in the middle of a quest. Just go to Quest Directory under Misc. and open the drive letter drop-down menu, but don't select anything. While the drop-down is still open, make ZC lose focus in some way (either by pressing the Windows key, or by changing to another application; it doesn't matter how). Once ZC has lost focus, you can't interact with it in any way. Your only choice at that point is to kill it using Task Manager.
EDIT: This was all done in windowed mode, not fullscreen.
I think this is related to the matrix hang: http://armageddongames.net/showthread.php?96639-Hang-Data-Corrpution-Windows-Adding-an-external-display-causes-hang
At least that's how I was able to reproduce it before. (eg; menu must be open.) EDIT: Actually, due to the finicky nature of trying to reproduce or debug these hangs, I'm not entirely sure ... as it's been a while. I'll have to take another quick look at it.
Also on Windows 7 64 bit running ZC 2.5 in windowed mode. I cannot reproduce this at all. I got it to go a little screwy after switching away from ZC and back as if the mouse was going haywire but after closing the menus it went back to normal.