I would say it depends on what type of a boat you are using. If you are kayaking and like to spend time in God's country, then hug the banks. But, be ready for some shallow water. On the lower western Pamlico Sound there are some Navy Bombing ranges with restricted waters.
Some of the Watertribe members are from North Carolina and paddle/sail this area.
See
http://sandybottomkayaker.blogspot.com/,
http://cs20dawnpatrol.blogspot.com/,
http://logofspartina.blogspot.com/,
http://www.microcruising.com/2006obx.htmThey all have articles within their Blogs about some of the cruising grounds around Pamlico Sound...