So I have been working on a bike route which I am calling the NationBuilders Bike Route (link here). The route is themed after Early American industry (Canals, Railways, etc.) and was inspired by my realization that by traveling the C and O Canal, then the Great Allegheney Passage trail, you would be pretty close to the Erie Canal and were starting to make a big loop along historical industrial routes that are also conveniently bike-friendly (about a third of it is on trails). For the portions that are not covered by the above routes, I use rail trails or Adventure Cycling Routes to patch the gaps. I have personally ridden about 75% of this route and can say that it contains some really great areas. The only problem is that the route is suprisingly long: 1500 miles (!).
The route basically goes like this, starting from DC (but you can start anywhere you want):
1. Leave DC on the C and O Canal heading towards Cumberland. The Canal is 183 miles that requires almost no riding on roads (hopefully they will raise enough to connect through at the Slackwater area). The trail is flat, in the woods, with occasional historical sites or small towns. I can't say enough good things about the canal - easily my favorite place to bike.
2. At the end of the Canal in Cumberland, MD, you can pick up the Great Allegheney Passage, which is a rails to trails crushed limestone path going about 140 miles from Cumberland to Pittsburgh. This is also a nice route - slightly easier rolling than the canal and slightly more civilization than the canal, but you have to pay for camping.
3. Next is the Pittsburgh section, which I patched together from the excellent and free Bike Pittsburgh bike map. Just outside of the city (Coraopolis), you pick up the route laid out in the Cleveland/Pittsburgh Connector (a map set available from Adventure Cycling). We use this route for 57 miles into the Lordstown area.
4. At this point, you can pick up the Western Reserve Greenway, a 42 mile rail trail that runs straight as an arrow north until it hits Astabula on Lake Erie.
5. At Astabula, you can pick up the Adventure Cycling Northern Tier route, which basically runs along the lake on decent biking roads. This route heads through Buffalo and into Niagara Falls (Well, not "into" Niagara Falls...).
6. From the Falls, you can continue along the Erie Canal all the way to Albany (350 miles). The Erie Canal has bike paths for some portions and local roads for other portions. Regardless, it is a nice ride through many small towns along a still-active Canal.
7. From Albany, I invented a 50 mile route along the Hudson River that takes you south to meet up with the Adventure Cycling Atlantic Coast route in Rhinebeck. From here, Adventure Cycling takes you through mid-state NY, Pennsylvania Dutch Country, and into DC (while avoiding NYC, Philly, and Baltimore).
I would really like to do this route at some point, but it is probably a good month of riding on a mountain bike. The one great benefit that the route has is that many (many!) people live close to it and could therefore do the entire trip without having to fly or ship a bike - you can just roll out from your house, then roll back in a month later!