Don't take the short route....
which will take you along the 401, I-81, I-90 and I-71 and will be generally flat and boring. If you can afford the time, look at roads which will bring you down the Appalachian Mountains to the old National Road through to the Ohio Valley. This would bring your through the Thousand Islands region, the Finger Lakes of New York (lots of waterfalls, gorges and wineries), central Pennsylvania (Grand Canyon of PA, Susquehanna Valley, Gettysburg), northern Virginia (various caverns), west through western Maryland and north central West Virginia (the old National Road and the Chesapeake and Ohio Canal if you stay north, The New River Gorge if you head south) and down the Ohio. Like TimboTA, I've driven parts of the Ohio (Huntington to Cincinnati) and it is a very relaxing and scenic trip between the major cities.
The reason I haven't listed specific roads as possibilities is that there are more roads through the regions I mentioned than can be listed and they are very scenic for the most part. And besides, what I think would suit my needs may not fit yours. Take a look at what's along the general lay of this route that appeals to you and go for it.
AZBuck