We've cruised extensively in boats of 30, 37, 40, 42, 57, and 79 feet. After the trip this past summer, we've done 115 locks. We've done pieces of the Great Loop from Fort Lauderdale to Mackinac both via the Saint Lawrence and the Erie. There's no question that offshore, longer and heavier is more comfortable, but on a Great Loop, I'd go for something in the low 40s unless you're planning on taking more than two or three people.
I'm well established here as one who wants a single conventional screw with full skeg. Particularly inland you need to think about protecting the prop and rudder. As for maneuverability, I can put Fintry (79', 150 tons displacement) and Morning Light (Webbers Cove 42, 20 tons displacement) anywhere I want unless the wind is blowing more than 25 knots or there's more than a knot of stern current. They both have bow thrusters.
Jim