Setting the hook is what happens at that moment in time after the fish has consumed your fly and you feeling that vibration on your line. It is here that many a fish is lost due to excitement, over-reaction, or incorrect response.
As with all types of fishing, many a hook set can be increased by simply sharpening your hooks. Most fishermen at the end of the day simply untie their fly from the line and store it back in the box. The next time out the fly is tied back on the line, ready to be cast again.
Each and every time you use a fly the hook point is degraded a bit. After every use you should wash the fly in fresh water, let it dry and then sharpen it a bit with a hook hone. You could do this on the way back to shore after a day on the water. This is also true of plugs.
A steel rasp sharpener can work wonders. Just a few strokes can put a sharp point back on the hook. You can also use a small whet stone as well. Remember that most hooks are triangular, so sharpen the three sides and then test it on you finger nail. If it raises a little material off your nail it is sharp.
In fly fishing you must be ready to control your outfit the moment the fly hits the water.
When I was first learning to fly fish, my mentor told me to cast with my dominant hand and then reel with the other. For example, I am right handed and so I cast with my right hand. This means my left hand controls the line. Once the line hits the water my right forefinger pinches the line to the cork and I take up any slack by reeling with the left hand. Or, I simply strip in the extra line and let it lie at my feet. But, as I strip in the extra line, it slides between the cork and my right forefinger.