Totally random. Sometimes it resets itself a mere couple of seconds upon entering a game, sometimes 30 minutes later. Some remarks though:
a) it always happens when I press space when trying to use something
b) I go fullscreen with F4 when entering the game but when it resets it goes back to the standard windowed mode.
c) I had the demo installed before I bought the full game. I deleted the demo before installing the full game but the reset bug/feature was also present in the demo. I thought it was just a mechanic built into the demo to stop people getting to far into the game. Like that 30 minute one shot RE2 demo is.
For now I am using that Rebalance patch and it has a built in save book so I can save states and still play the game. Not going to do rouge-likes if the game keeps randomly resetting itself.