If they can make a movie out of Scott Pilgrim, they could make a movie out of Questionable Content, but of course, with that title, they'd have to raunch it up a bit more than Jeph might like for distribution purposes.
As for the suggestion of Anna Paquin for Hanners... After seeing her get her row plowed by a creature of the night that just rose up out of the cold, wet earth, I've gotta veto that idea.
As for the location, since Smif is an analogue of Smith and Smith is in Northampton, MA, then the setting for QC is an analogue for Northampton. QED