When you consider that you are going to false cast 2-4x when throwing dry flies for every one time you cast a spinning rod, I would definitely say that fly fishing drys is more fatiguing. Nymphing may be another story. A roll cast here and there isn't as much work, so I would call it a tie with using a spinning rod. Streamers...don't know, too much work for me. I always figured that if I had to retrieve a fly like that I might as well use a spinning rod.