In a large bowl, whisk together 1 cup buttermilk and 2 tablespoons hot sauce. Add 4 boneless skinless chicken breasts, making sure they are completely submerged in the marinade.
Cover and refrigerate for at least 2 hours, or overnight for best results.
In a separate shallow bowl, combine 1 cup all-purpose flour, 1 tablespoon paprika, 2 teaspoons onion powder, 2 teaspoons garlic powder, ½ teaspoon cayenne pepper, 1 teaspoon salt, and 1 teaspoon black pepper. Mix well.
Remove the chicken breasts from the buttermilk mixture, allowing any excess marinade to drip off.
Dredge each chicken breast in the seasoned flour mixture, coating all sides thoroughly. Shake off any excess flour.
Pour enough vegetable oil into a large skillet or frying pan to reach about 1 inch deep. Heat the oil over medium-high heat until it reaches 350°F.
Carefully place the coated chicken breasts into the hot oil. Fry for 6–8 minutes per side, or until golden brown and cooked through. The internal temperature should reach 165°F.
Transfer the fried chicken breasts to a paper towel-lined plate and allow excess oil to drain.
Spread mayonnaise on the cut sides of 4 toasted hamburger buns.
Place 1 fried chicken breast on the bottom half of each bun.
Top each sandwich with lettuce leaves and sliced tomato, if desired.
Place the top bun on each sandwich and serve immediately.
Notes
For the most flavorful and tender chicken, marinate the chicken in the buttermilk mixture for at least 2 hours, or preferably overnight.