I recently toured Ostia Antica, and the guide said that while the Tiber ran next to the city in ancient times, it no longer does. She added that this change happened "in one night." I took it to mean that there was a single great flood that resulted in a large change, but Google isn't pointing me toward such a flood. Was the course change more the result of multiple floods, or was there one flood larger than the others?
I have never heard of anything like that before. The course change of the Tiber is, as far as I know, entirely attributable to the natural processes that many rivers undergo. Silting, collapse of banks, and such can have profound changes, sometimes even season to season.
That said, the Tiber still does run next to Ostia. The biggest change is that the coast has silted over the years, pushing the coastline out and thus leaving the ancient city a ways inland.