Like other say, it's mainly time consuming. It punishes you the most if you're careless and unprepared, otherwise, taking it slow and taking precautions is the best way to proceed. It's really not something that most people would necessarily enjoy, as the game is balanced around portals due to the sheer scale of the map, along with it's other mechanics. I think it'd be alright to try it once at least, though you do need some time and patient on your hands.

And Mistlands will most likely be a problem, i'm not a 100% how people do navigate it, but i'd imagine using the wisp torches, smoke from the fire and "breadcrumb" trails are some.