USB + Power: Isolate or not?
http://www.analog.com/en/interface-isolation/usb-isolators/adum4160/products/product.html

USB is a bidirectional differential bus, and will be hard to brute-force isolate with optocouplers.  I'd recommend purpose-built IC's to do the job for you.  I've been happy with the ADUM line, though I haven't done USB isolation.

As to whether you need to isolate or not, we'd have to know much more about your application.  There's no reason per se why you would need to isolate just because you're using an external supply in addition to Vusb.  That said, I've used unisolated USB audio interfaces that I sure wished were isolated.