1. Preheat oven to 350°F (175°C) and lightly grease a 9×13 inch (23×33 cm) baking dish.
2. Mix ketchup and half of the barbecue sauce, and set aside.
3. In a large bowl, combine ground beef, crushed crackers, onion soup mix, eggs, salt, pepper, garlic powder, and onion powder; mix gently but thoroughly.
4. Press the meat mixture evenly into the prepared baking dish as the base layer (about 3/4 inch thick).
5. Spread uncooked macaroni noodles evenly over the meatloaf base.
6. In a bowl, whisk together milk and condensed cheddar cheese soup until smooth, then pour over the macaroni layer to coat all pasta evenly.
7. Sprinkle 2 cups of the shredded cheese blend over the macaroni and cheese layer.
8. Cover the casserole tightly with foil and bake for 50 minutes.
9. Remove foil, spread the reserved ketchup-barbecue glaze evenly over the casserole, then top with the remaining 2 cups of shredded cheese.
10. Bake uncovered for an additional 15-20 minutes, or until the cheese is melted and slightly browned on the edges.
11. Let the casserole rest for 5 to 10 minutes before serving to set.