In a large bowl, combine buttermilk, garlic powder, onion powder, paprika, salt, and black pepper. Add the chicken thighs and ensure they are fully submerged. Cover and refrigerate for at least 1 hour or up to overnight for best flavor.
In another bowl, mix together the flour, baking powder, and cayenne pepper (if using).
Heat about ½ inch of vegetable oil in a large skillet over medium-high heat until it reaches 350°F.
Remove the chicken from the buttermilk, allowing excess to drip off. Dredge each piece in the flour mixture, pressing lightly to ensure an even coating.
Carefully place the coated chicken thighs in the hot oil. Fry for about 5-7 minutes on each side, or until golden brown and cooked through (internal temperature should reach 165°F).
Transfer the fried chicken to a paper towel-lined plate to drain excess oil.
Toast the hamburger buns lightly in the skillet or oven if desired.
Assemble the sandwiches by spreading mayonnaise on the bottom half of each bun, adding a piece of crispy chicken, lettuce, tomato slices, and pickles. Top with the other half of the bun.