The problem for me living on the east coast is the interesting part of the trip would be in the west. If I ever do a long distance Amtrak it would probably be Denver or Chicago to the west coast.
I've done some of those and can say - east coast to Chicago or just a bit beyond is pretty interesting.
And west coast is great, starting somewhere after the plains.
The plains are really boring - unfortunately I've not kept up with schedules, but if you can get the overnight to mostly be in the plains, you've something.
But on the east coast maybe you can take advantage of Amtrak's only profitable long-distance route! The Auto Train! wooohooo
No interest in Florida :-) Not that I go down to NYC much these days but have taken the NE Corridor/Acela many times which is a nice enough train ride (and not super-long). Love going in and out of NYC. Taking the train up at tail-end of a May trip from overseas.
Thanks for the info. I'd probably do at least some section of the Empire Builder or Zephyr if I did a long distance run.
I have found that a great "in the US" vacation can be to fly out to your destination, do your vacation, and then take the train back. If you leave a buffer day you won't even miss work, and you'll arrive much more refreshed than if you flew in (at least in my experience).