Preheat the oven to 375 degrees F (190 degrees C).
For meatloaf, melt butter in a skillet over medium heat, and cook the onion and garlic until the onion is translucent, about 5 minutes.
Combine onion mixture, beef, crushed crackers, egg, sour cream, Worcestershire sauce, 1/2 can tomato sauce, onion powder, salt, and pepper in a large bowl. Mix until well combined. Transfer mixture to a 9x13 baking dish and spread into an even layer. Set aside.
Combine remaining tomato sauce, ketchup, and barbecue sauce in a small bowl. Spread sauce evenly over meat mixture.
Bake in the preheated oven for 20 minutes.
Meanwhile, for mac & cheese, bring a large pot of salted water to a boil; cook macaroni until al dente, 8 to 10 minutes. Drain, and return to the pot. Set aside.
Melt 1/4 cup butter in a saucepan over medium heat. Whisk in flour. Slowly pour in milk while continuing to whisk. Once milk is heated through add cheese, 1 cup at a time, continuing to whisk, until cheese has melted and sauce is smooth. Season with salt and pepper.
Pour cheese sauce over noodles and stir until noodles are well coated.
For topping, stir melted butter and panko together in a small bowl; set aside.
Once meatloaf comes out of the oven, pour macaroni over meatloaf in an even layer. Top evenly with panko mixture.
Return to the oven; bake until bubbly and golden brown, 10 to 15 minutes. Remove the dish from the oven and allow to cool for 5 to 10 minutes before serving.
