The best throttle response is with a short and direct back pressure line from exhaust to tank, the shorter the line the directer the throttle.
The problem you can face is that there is no pressure chamber in the system when the tank is compleetly full. The pressure pulses can come at the wrong moment casing the engine maing hickups. When some fuel is used a pressure room above the fuel is created picking up the pressure pulses storing it to a more constant pressure.
Today's tank caps do have a small chamber taking away that problem but if it still exist yo need an extra chamber.
The exhaust cooler does lower the temperature of the gasses a tiny bit and with that also the fuel in the tank. It is not much but it makes the engine tuning more consistent. With that it is possible to search a better limit on the lean side making a better milage.
Then there are devices to adjust the pressure or a device as the TeamOrion CPD. These tools do soften the pressure so you have to change the needles on the carburator to get the characteristic of the engine right. One of the bad things of a normal setup is that going from full throttle to idle the huge pressure is giving a boost of fuel into the engine at a moment you do not want it resulting a rich moment when touching the throttle again. In this situation trying to lean that out can cause a fuel shortage on other moments.
Lowering the pressure or filtering out such pressure boosts will give a much directer reacting engine and also some extra milage.
Speed is only fiction but a 130+km/h MRS4 is for real.