Route 50 runs all the way from Sacramento to Ocean City, MD. I tried riding it from East to West about a year ago, but had to leave Rte 50 in Colorado because of snow (it was mid march), and head further south.
From MD to Dodge City KS, where I left Route 50, there was very little traffic and you get to see plenty of small town America. I made pretty good time, and it beats the hell out of the interstate.
That said, depending on how much time you have, it would be a real shame to cross the US and miss all of the cool national parks, which you would have to zig-zag to get to. Also, my favorite part of the country is NorCal-Oregon-Washington-Idaho, so maybe start by going north, not east?