I've been running my web-server Raspberry Pi (the Pi that's running this website, in fact) via a 128GB Sandisk USB nub (the little USB stick) and it's been great for the storage aspect. The best part was how easy it was to set up.
The only real reason I'm writing this is to share with you the pitfalls that I ran into and didn't find out until after they happened to me.
First things first, I used the "official" RaspberryPi.org How to boot from a USB Mass Storage Device on a Raspberry Pi 3 tutorial to get this thing going. It's easy to follow and it works.
At the end of their tutorial they note,
After between five and ten seconds the Raspberry Pi 3 should begin booting, and display the rainbow splash screen on an attached screen.
Note that this is best case scenario. Mine takes literally about 30-45 seconds to boot. That is the single pitfall that I've found. On a side-note to this note you won't (at least I don't) see the normal green light blinking when the Pi is accessing the USB stick. Instead you'll see a constant one-second blink. Nothing fancy.