Cover chicken with buttermilk in large bowl; refrigerate at least 2 hours or overnight for best results.
Combine flour, paprika, garlic powder, onion powder, pepper, salt, and cayenne in shallow dish to distribute spices evenly.
Heat oil in large deep skillet or Dutch oven to 350°F; maintain temperature with thermometer.
Remove chicken, letting excess buttermilk drip off; dredge thoroughly in flour, pressing to coat well.
Carefully add to hot oil without crowding; work in batches if needed. Fry 12-15 minutes, turning once, until golden brown and internal temperature reaches 165°F.
Drain on wire rack over baking sheet; rest 5 minutes to redistribute juices before serving.