usb drive for main storage

This Silverstone ML05 will be very crowded soon. My pc storage hovers around 50-75Gb. Can I ditch the HDD or SSD for a 3.0 usb key drive of 128 Gb or so for my storage. I am Win 10 now. I don't game or office, just mail,shop, etc. Oldie, but still newbie. I have more questions than answers, so...