Hah! Nice. I tried to do this a while ago with MX Linux. Biggest thing IIRC was to disable swap and tune disk/buffer write sync thresholds, both so you're not burning too many write cycles and also so applications can get away with writing to "disk" without stuttering on IO across slow USB ports.

The usefulness day-to-day is pretty limited, however, assuming you're just carrying it around and also have access to proper installations.