In a medium saucepan, melt the butter over medium heat. Add the chopped onion and sauté until slightly softened, about 5 minutes. Stir in the ground beef, Worcestershire sauce, salt, pepper, and garlic powder. Cook the mixture, stirring occasionally, until the beef is browned and crumbly, about 10 minutes. Once cooked, remove the pan from heat, drain any excess liquid from the beef, and allow it to rest for about 2 minutes.

While the beef is resting, preheat a griddle or flat skillet over medium heat and coat it lightly with cooking spray.

Place one tortilla onto the hot griddle. Layer with a portion of Colby cheese, followed by 1/4 of the cooked beef mixture. Drizzle 1 teaspoon each of ketchup, mustard, and sweet relish over the beef. Sprinkle with more Colby cheese and place a second tortilla on top. Gently press down to flatten the quesadilla.

Carefully flip the quesadilla using a spatula and cook for another 3 to 5 minutes, or until the tortilla is golden brown and the cheese is fully melted. Remove from the heat and cut into four wedges. Repeat the process with the remaining tortillas, beef mixture, cheese, and condiments.