The Mass Effect Community Forums have word that Mass Effect 2 will span two DVDs for both Windows and Xbox 360, and the Xbox 360 version will require a one-time disc swap (thanks Kotaku). Word is:

Ok some details for you.

1 - Yes, there are 2 game discs for both the PC and Xbox 360 versions, both the Collector's and standard editions.

2 - There is a 3rd disc with the Collector's Edition. This is a movie DvD containing making of and other bonus information.

3 - The PC version is a standard install. You install the information from both discs and then play with 1 disc in the drive. No swapping.

4 - The Xbox 360 does not have an install and does require disc swapping during play.

5 - Even though there is a disc swap, it occurs at a carefully planned place in the game (that does not interfere with gameplay) and is done once. You do not swap back and forth. 1 swap and then done.

6 - Why 2 discs? Answer: Because you cannot fit this much awesome on one disc.

Hope this helps.