Central hubs such as Bad Dürkheim or Neustadt make good bases for exploring the region, although the cities along the Rhine are livelier, particularly Mainz. Driving the Wine Road takes longer than you might expect, and will probably involve spur of the moment stops, so you may want to consider a stopover in one of the many country inns en route.
When traveling with children, Neustadt or Worms are convenient bases from which to explore nearby Holiday Park.