Bring water and milk to boil in medium saucepan over high heat. Stir in macaroni and reduce heat to medium-low. Cook, stirring frequently, until macaroni is soft (slightly past al dente), 6 to 8 minutes. Add American cheese, mustard, and cayenne and cook, stirring constantly, until cheese is completely melted, about 1 minute. Off heat, stir in cheddar until evenly distributed but not melted. Cover saucepan and let stand for 5 minutes.

Meanwhile, combine panko, oil, 1/8 teaspoon salt, and 1/8 teaspoon pepper in 8-inch nonstick skillet until panko is evenly moistened. Cook over medium heat, stirring frequently, until evenly browned, 3 to 4 minutes. Off heat, sprinkle Parmesan over panko mixture and stir to combine. Transfer panko mixture to small bowl.

Stir macaroni until sauce is smooth (sauce may look loose but will thicken as it cools). Season with salt and pepper to taste. Transfer to warm serving dish and sprinkle panko mixture over top. Serve immediately.