There's probabally other limitations, but as I understand it one of the limiting factors is takeoff and landing speed. Even on a good day and in a still harbor, water is pretty bumpy, which means you need to be out of it at a pretty low speed. This leads to all sorts of tradeoffs elsewhere in the airplane design (mostly, again - as I understand it, in wing design) that hamper the airplane in other ways.

In the end, it's more practical to deal with the problem of finding an airport (after all, there are a lot of airports) than to solve the other problems of making a large sea plane.