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Setting the game to fullscreen instead of windowed let me play it for an hour before it hard crashed my computer.

Fre7: I have the same problem and the solution described above doesn't work for me.

It seems to me like the configuration tool isn't saving the settings, as every time I launch the tool all the settings have been reset. This could explain why the solution doesn't work.
This pretty much explains your issue. Either the folder you're trying to save to isn't writable or you don't have the permissions. Also remember to clicks save, it doesn't autosave... I think.
A few people, myself included, have had a similar problem: disabling target rendering allowed the game to run in my case.
I'm having this issue, and the game was sent to me as a gift from a friend, so didn't have any clue this was an issue. :( Tried everything above with zero luck