I currently have a region of 49 large cities (flat plains). It is over 1GB.
I keep the video settings on as low as possible and it runs fairly well.
I incubated a gridopolis city in a 1 city region until it reached 725,000, then imported 49 copies into the large region. When the center city reached 2,000,000 after bouncing back and forth between its neighbors, I imported it back into the 1 city region. I then imported 48 copies to fill the big region, of which there are now almost 100,000,000 residents. With everything so dense, the fastest speed is noticeably slower, but still playable. I don't think the region could get much larger, though.
I have a 64-bit Windows 7 computer with
Core2 Duo @ 2.0 GHz
4GB of RAM
Nvidia GeForce 9600 GT