I am in Ohio and my riding partner is in Georgia. As far as locations - we would probably drive. I have thrown out the northern plains - somewhere in Montana even - as an option.
I did have the thought of doing a combination train/bike trip - ride out and train back, or train out and ride back.
We're already pretty far apart between where our home-bases are, so traveling isn't much of a concern there.
I have seen some videos of off-road touring. That is much more my style, from the backpacker in me, but from a bike perspective I don't think either of us have the right set up to attempt that. However, I don't want to exclude it - the more wilderness the better, if we can access it with the bikes we have = maintained trails/established roads that aren't too wet, rutted, or pot holed.