Well, you can hit stonehenge in one of two major directions. Both ways take you to Birmingham from Manchester, and then split west (towards bristol) and east (towards london). Stonehenge is basically in between Bristol and London, about 20 minutes or so from the major motorway between.
It wouldn't be my best idea for a daytrip from Manchester, that's for sure, and is best done in combination with a trip to Salisbury (cathedral, etc) and a trip to see the white horses... using either Bristol (Bath!) or London as a home base.