Some more things:
- You should send a private Message to Will
and link to this thread.
- You could try running, let's pick Sam & Max Season 1 Episode 1, with this prefs.prop
Unzip it and copy it to "C:\Program Files\Telltale Games\Sam and Max - Season One\Episode 1 - Culture Shock Data" or similar, if you installed individual episodes.
Now for some stupid guessing:
- Have you recently installed any new hardware?
- Have you tried running the game removing all nonessential Hardware (e.g. USB devices)?
- Have you tried changing your screen resolution?