I will initially segment design and prototyping into a base motherboard that contains the CPU & RAM with add-on boards for peripheral functions (i.e. Wi-Fi, BT, flash storage, etc). The theory here is that I can get comfortable with each peripheral function without having to spin a new board that contains everything each time I mess something up. After I get everything working, I will then design a single board that contains everything.
I'm going to start this project, and hopefully finish, by only using KiCad and OSH Park. I want to see how far I can get with open source and what tools and suppliers are easily available to the maker and hobbyist community.