Water temperature will play a big role in when to set the hook for rising fish. Needless to say, the strike in the winter will be exagerattedly slow while during the warmer summer months, the fish may strike very quickly. In my opinion, the best time to set the hook is when the fish has just taken the fly and started to submerge itself. It is at this time that the fly is squarely in the fishes mouth.
Another trick is to take the hook, and right at the bend, offset the point of the hook buy about 20 degrees or so. This offset will provide a better angle to hook into the fishes mouth. (Gomakatsu octopus hooks are a prime example.)
Sometimes, very small fish will come and crash your fly and may make you believe that some larger fish is actually in pursuit. These small fish simply may not have mouths large enough to grab the fly.
Last but not least, make sure that the hooks have been sharpened. Dull hooks lose many fish. Take time every few minutes to make sure that the hooks are sharp enough to stick to the back of the thumbnail when dragged along. If they don't bite in, they are not sharp enough. This is critical.
Best of luck,