Having a patchwork assembly of differing state and local regulations and restrictions to follow while in the air would absolutely affect interstate commerce. There's really no good rational argument against that.
Yet we have just such a patchwork assembly of differing state and local regulations and restriction to follow while on the roads: Speed limits and rules for setting them, turn restrictions, stop and yield sign placement, various rules of the road and its amenities (turn-on-red, where - if at all - U-turns are legal, lane-change frequency restrictions, lane restrictions on trucks (and no-truck routes), passing on the right, maximum durations at rest stops and activity there (such as sleeping or cooking over a fire), and a host of other rules - not to mention their enforcement) all vary from state to state.
It's dependent on each state's government(s) to pass the individual regulations. Yes, there's a lot of standardization, and following federal rules. But the federal rules are followed voluntarily when it's in a state's interest, enforced as a condition of federal funding for construction and maintenance of roads bearing US or Interstate route designations, or encouraged by federal blackmail composed of the withholding of the state's share of funds gathered by the federal gasoline taxes.
Any argument that flying at all is interstate commerce goes double for driving - where long-haul trucks, passenger cars, and even bicycles and pedestrians share common roads. So why does the Federal government have to blackmail the states into legislating their way for regional and local roads, yet can claim it has the right to totally control flight, not just of interstate traffic and/or at interstate altitudes or in the glidepaths around federally-funded airports, but of battery-powered gadgets, with range far to limited to reach a state border from most parts of a state, lighter than the average dog, and all the way down to the grass in your back yard?