Dust may be an issue. My plan for that is to have the air intake be at the bottom and use magnetic meshing to act as an air filter so it’s easy to take out and clean.
I haven’t really considered liquid cooling as a primary concern. Due to the size of the system, some sacrifices are required in the choice of components. For one, full sized graphics cards will not be compatible. I think an all in one 120mm liquid cooler will fit though.
Portability is a bit of a tough one. There’s a pretty big range of use cases. Anywhere from people that need to move their computer often in their home or office, people that occasionally need to bring their computer with them (mobile workers, LAN parties) all the way to people that are constantly traveling and need the power of a desktop (A/V production, location based trades…). I’m aiming the first two categories. People that want a clean looking desktop that facilitates mobility.
When moving around my small ITX system, I’ve came across two major issues I hope to have solved with my current design. As you mentioned, moving the peripherals is a pain. I find myself putting my wireless keyboard and mouse on top of the case but it’s flat and smooth so then end up sliding off to the floor… That’s the reason for the lip up top, you can put your mouse and other knick knacks in that pocket if you’re just moving from room to room. I also, found the back end of the system with all of the IO has a lot of exposed fragile parts like dongles, wifi antenas and just little cutouts and ports. The pipes at the bottom naturally cover up that fragile part. Also, once you put the computer in a bag, it creates a zone that’s safe from crushing to put other peripherals.