The necessity of two discs may mean a staggering amount of content for the RPG sequel -- the original was certainly no slouch in content. While some may lament the necessity of having to get up at least once during Mass Effect 2, Priestly promises that the disc swap happens at a dramatically appropriate point in the story. "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."
We're going to fathom a guess as to when the swap will occur: immediately after the "suicide mission" revealed in the game's initial teaser.
[Thanks, Darth B.; Via Kotaku]