I am running 6/3 NMB cable from my main to a 50 amp sub panel in the backyard. The total run is approx. 60 feet. Most of it will run through my attic, but about 20 feet will run through the garage. Can I feed the garage portion through pvc or aluminum flex on top of the rafters to protect it. If so, which would be better?

If the cable is above the rafters, why the need to protect it there? In any case , yes you can use conduit to protect it. PVC would be fine.

You must be planning to store junk on top of the rafters like most of us. In that case the cable should be protected or stapled on the side of the rfaters.