1. Run PixelMonitor.
2. Crosshair cursor appears; click or drag to select an area of your display for the program to monitor.
3. As soon as a single pixel in selected area changes*, a sound plays to alert you of the change. [and/or an alert window pops up, etc]
* (preferably this could ignore the mouse cursor floating by)
This would be great for letting you look/step away from your computer to, say, make your bed while you're waiting for some change in a program without a built-in alert system.