Well, all these replies, and no one has described what I do, and I feel my methods are superior to those listed so far. Hmmmm... Maybe I should only share this method with trusted members, and give it a name. How about "the possum pop"? BWAHAAHAHAHA!!!!
Seriously, there's no need to close it on your leg, or shift hand positions halfway closed, etc. Here's what I do.
For a mid lock design, start out holding the knife edge up, and just press the lock bar with the inside base of your middle finger. Once the lock is disengaged, close the blade with your index finger on the spine. You can move your thumb out of the way in one motion as the blade is closing; there's no need to stop the blade halfway, shift grips, and finish the close. You should be able to easily flip the blade open and back closed again in less than a second.
For a rear locker, the idea is modified a bit. Instead of pressing the lock bar with your middle finger, you'll use your pinky. But since the pinky doesn't have the needed strength or dexterity, you have to curl your pinky up, and press the bar with the back of your finger, while your 2 middle fingers and thumb hold the handle. (well, actually, your pinky doesn't move; you use your other fingers to press the handle & lock bar against the back of your pinky.) It's easiest to position your index finger on the spine first, so once the lock bar is disengaged, you can easily flip the blade closed in one motion. If the handle scales are thick enough to hang onto, you can do all this without your fingers ever getting in the blade's path. Thus, once again, you can safely close the knife in one fluid motion without ever shifting your grip or stopping the blade halfway. It's even quicker than with a mid- locker; you should be able to flick the blade open and closed in half a second with practice.
Best.
-the possum