There are a ton of good places to go in the southern bay. I have an uncle that docks in the Salt Ponds. From there you have a ton of options.
Deltaville is a good overnight trip. It is a neat town and the anchorage in Jackson Creek is nice. There is access to a town dock and you can then walk or bike ride into town (if you carry bikes). There is a good sail maker, canvas makers, West Marine, and cool places to eat.
Tangier Island is a must see. It would be a good overnight trip as well. What makes it unique is that it is an island in the middle of the Bay that is accessible by boat or small plane. It is a water-man's community but it has interesting shops.
Onancock is a cool place that is on the Eastern Shore. It is a neat little town. It is a bit of a haul to get through the channel through there because you will pass about 50 nav markers (if I remember correctly).
Kiptopeake is a state park across the bay from Hampton. It is a man made area to anchor that has sunken barges to provide an area to anchor. This anchorage can have swells if the wind is out of the North West.
There are a lot of other nice places to go such as Solomons Island, Smith Island, Chrisfield, and Indian Creek. You can also go out of the bay to Rudee Inlet and visit Virginia Beach that way.