Caveat: I'm in the Northeastern section of the United States so these tips will not apply to everyone.
Step One: Join the Toys'n'Bricks forum. These people are serious bargain hunters and they talk about sales and availability of Lego sets constantly. Don't be a leech! Contribute where you can and let people know your location when you post about finding a deal.
Step Two: Figure out which stores in your area carry discounted Lego sets. Target and Walmart are two stores in my area that put Lego on clearance on a regular basis. Marshalls and T.J. Maxx are two more in my area that both carry a limited amount of older/discontinued of Lego.
Step Three: Keep your eyes open. You have to visit stores on a fairly regular basis. Get to know their stock. Understand when things get rotated into clearance.
Step Four: Know when the big clearance "seasons" are. Just after Christmas is always good for getting deals, especially at the Lego store. Target has a summer clearance session.
Step Five: Watch out for stores that are moving locations or remodeling. Companies don't like to transport a lot of stock between locations when they move, they also like having room for remodeling so this leads to stock being discounted or clearanced to accomplish these goals.
Step Six: Be careful. A lot of stores initially put items on "clearance" at regular prices. Be willing to wait until the prices drop. Also, be willing to wait for prices to drop below the $0.10/piece "golden ratio".
Step Seven: I've found -- through personal experience -- that if something is a good deal, I want it, and I don't buy it, it will not be there when I go back later. Don't be afraid to pull the trigger on a purchase.
Good luck and good hunting!