Different regions seem to be more reachable by bus, others by train, sometimes the cheapest way is a discount airline. I am trying to put together an itinerary that takes advantage of these various affordable modes of travel. At the same time, I am also trying to avoid long stays at expensive locations which can happen if you are waiting for a flight.
Also, the timing of travel can be a huge consideration. I want to avoid peak season for cost reasons but might prefer shoulder-season because sometimes off-season makes for dangerous roads. Anyway, the travels might need to be broken into several parts to wait for better weather in the next region.
I realize this is a huge question, but I am trying to gather a general plan then maybe I can break that down by region once I figure out what the regions are. I imagine in some places you can rent a car and visit 20 countries in a big loop. Other areas are only practicably accessible by plane.
I guess the other constraint is that I have waited until late in life, so biking the whole way is no longer an option, but I am planning to travel with just a backpack and am willing to give up a good bit of comfort for the opportunity to see more places.