Earlier quoted context omitted.
Since the Pi people finally got USB boot finished for the Pi 4, I'm not sure what USB annoyances are left to worry about? That's really why I asked the question. A USB 3 SSD seems about as trouble-free as a storage device can possibly be.
A M.2 SSD is more trouble free. I recently built a desktop computer. It uses a 6x6 inch mini-ITX motherboard. The motherboard has a CPU and 2 sticks of RAM in it, raising the height to about 2 inches. The SSD goes inside the motherboard in the M.2 slot. Aside from this 6x6x2" unit, the only other things are: - the gigantic graphics card - not necessary on these type of computers - the power supply unit - standard USB…
> having a large external USB SSD with a cable to connect.
The Samsung t5 and t7 SSDs I'm using with RPi 4s are about the size of a credit card (a stack of five credit cards, I guess). The tiny, very solid flirc cases for the Pis aren't much bigger, and dissipate heat beautifully. I like this solution a lot more than I anticipated I would.