Is it possible to run League off of a USB?

Yes, people at my college do it all the time.

to run LoL from your USB. You must copy files --> then to launch it go to the Rads folder --> projects folder --> LoL launcher --> releases --> (patch number etc.. folder) -- > deploy --> LoLlauncher.exe This was the only way i could launch the game on the computers at USF.

Note: The ingame play seemed fine, normal latency, normal fps. I noticed when I adjusted the volume settings and press ok (to apply the settings) there was delay due to which i believe the speed b/t the computer to USB interaction. Also, I have noticed after playing the game I could not safely eject the USB flash drive because it said generic volume device was still in use. After this, I just kept removing it - now it says that there is a probably with device in which it says the USB needs to be scanned. I just continue without scanning however, I may purchase another smaller USB just for LoL itself in order to prevent possible data loss for my USB for school.