Cook ground beef and onion until meat is no longer pink and onions are tender. Drain well. Add spaghetti sauce and simmer for 10 minutes.
In a 13 x 9 inch baking pan (the deeper, the better) place half of the rotini, half of the cheddar, half of the sauce mixture, half of the mozzarella and top with a layer of pepperoni. Repeat layers and bake covered at 350 degrees for 1 hour.