So in short:  reboot.

http://support.microsoft.com/?kbid=952709

This is actually kind of funny.  The fix for Vista was only published a week ago.  There is apparently a memory leak of some sort that causes Windows to stop loading large executables.

Here is the funny part of the KB article:

This update improves the reliability of Windows Vista SP1-based computers that experience issues in which large applications cannot run after the computer is turned on for extended periods of time. For example, when you try to start Excel 2007 after the computer is turned on for extended periods of time, a user may receive an error message that resembles the following:

EXCEL.EXE is not a valid Win32 application

Sorry Microsoft.. I normally have your back but this is a monster of a quality miss.