As you might be able to guess from the name, 6 Differences is a followup to 5 Differences (below). There's not terribly much difference between the two -- certainly the basic principle and the whimsical attitude are both still quite present -- but there are a few differences (no pun intended).
6 Differences features photographic images (in this case, of night scenes) rather than the rotoscoped images of 5 Differences. This often makes it somewhat more difficult to pick out the differences. (However, the changing differences feature of 5 Differences appears to be gone, as the differences are the same each time, as far as I can tell.) Animation also plays a heavier role, as many of the different elements are moving. There's also some pleasant background music available which fits nicely with the game. Time also plays a larger role -- there are some differences that don't become apparent until other things have happened. Finally, sometimes the two panels are reflections of each other, which adds a layer of difficulty. As compensation for the additional differences, there's also a hint feature, which reveals one difference. The interface is still non-existent, alas.
Despite these changes, this is still pretty much the same game, and an enjoyable way to spend twenty minutes or so (depending on just how skilled you are at difference-finding).