Proseries data, like QuickBooks data cannot sit in Dropbox or similar since it is an open database file. 

I have use RAID (Redundant Array of Independent Disks) on my computer for years as another method of backup (if one hard drive goes bad the other one is available and up to date) and I've let the computer experts set it up.  Never had to use it so I "assume" it works. 

My suggestion is to open the file from the main hard drive and only use backup in case of need.  But, yes you can put a client file on a USB drive and operate from there with no speed differential - obviously USB 3.0 is faster than 2.0 and faster than 1.0.