Preheat oven to 400 degrees F. Grease a 9x13 inch baking dish (or 3 qt baking dish) and set aside.
Boil pasta, according to package directions, in a large pot of water. Be sure to add a generous pinch of kosher salt to the water, as it will flavor the pasta. Drain pasta, reserving 1/2 cup of pasta cooking water. Lightly drizzle drained pasta with a little olive oil to keep it from sticking and add it to a large mixing bowl.
While pasta is boiling, add ground beef and brown over MED-HIGH heat, breaking up the meat into crumbles, until cooked through, about 4-5 minutes. Add onion and chili powder to the ground beef and cook another 2-3 minutes. Depending on how much fat is rendered from the beef, you may need to drain it at this point.
Add salsa to ground beef skillet and stir to combine. Add to the cooked pasta in the mixing bowl.
Add butter to a medium saucepan and cook over MED heat. When butter is melted, add flour and whisk to combine. Cook 30 seconds, then slowly whisk in the milk, a little at a time, whisking as you add it. Cook until thickened, then stir in 2 cups of the cheddar cheese and 1 cup of the pepper jack cheese. Stir in black pepper, kosher salt and oregano.
Pour cheese sauce into the large mixing bowl with the meat mixture and pasta. Stir to combine. If mixture seems too thick, add a little bit of the reserved pasta water. Add in 1/4 cup each of the cheddar and pepper jack and stir to combine.
Transfer pasta to the prepared baking dish, top with remaining cheeses (1/4 cup each of cheddar and pepper jack). Bake for 12-15 minutes, until cheese is melted and bubbly.
Serve hot, garnished with fresh parsley or cilantro.