I've recently picked up Uncharted: Drake's Fortune from the Amazon "bargain bin" and have been playing through it. Quite a fun game, actually, but I've only managed to get to Chapter 10 ("The Customs House"). The chapter's opening cutscene finished and I started to run towards the stairs inside the customs house when the game locked up completely. No PS menu key response, no Start response, etc. The PS3 required a full restart.
So I ejected the disc, buffed it for fingerprints (negative), examined it for scratches (negative) and loaded up again thinking that the glitch was perhaps temporary. No such luck. This time, the game loaded me in post-cutscene and I managed to get a few steps up the stairs before it froze again. Same effect, same remedy. I tried a third time, got to the room at the top of the stairs, and POOF, another freeze.