The biggest challenge in my mind are the legions of cheaters who want to game the system (i.e. not doing the work/taking the tests themselves). I mean, this isn't much different from real, physical college, but at least in real, physical college it can be a bit more difficult to do.
I'm currently enrolled in a real credit-granting/transferrable class at edX. I'm personally learning a lot (or, rather, relearning), but I can tell there's a lot of students, based on the discussions, who really aren't up to the level that the class requires*.. This will also always be an issue. I can't imagine what the drop rate looks like.
*meaning if there's a job on the line, it would encourage some folks to engage in less than honest methods to achieve the grads, rather than seek the knowledge