It would help.
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Doing something like this with the radiator can keep you cool on the street and help with your drag reduction. Look at the ducting the kit cobra guys do, they even angle the radiator to get a bigger core and still help with drag.
Anything air touches is "wetted". Reducing "wetted" area will reduce drag a whole lot. Reducing the air going through that pig trough of a front end will net big gains.
Bug deflectors act like wings. They probably won't reduce drag, since they create turbulence. That causes what's called induced drag, and it has a similar equation, but the same result: keep it smooth.
A cover which started at the top of the cab and ended at the tailgate would be best, but won't look stock. A decent camper shell could net similar gains. An under truck belly pan with a diffuser to help fill the void behind the tailgate and shell would probably be a net gain. The shell would need to be smooth and the rear glass should angle forward (toward cab). The top of it would preferably slope down slowly too, to mirror the rear diffuser to some extent.
Remember, when you change the direction of air, you're applying an equal and opposite force to the car. If you deflect wind up, car go down, if you deflect wind down, car go up. So you typically try to minimize changes in direction.
Stagnation areas cause drag, but can also be a benefit, since you're balancing wetted area and wind deflection. Remember the big flat face semis? They existed for a reason... It's still a trade off though, one isn't going to be a huge difference with another, but you can stack benefits in the direction you're designing.
A closed off grill with duct work for radiator air, a belly pan, smooth shell, a filler panel between the cab and bed, and smoothing all the trim, hinges, door gaps, drip rails, windscreen trim, etc will all add up. How much it adds up will depend on the MPH you're already attaining, or expect to. I don't think the juice would be worth the squeeze. At 125+? Probably some gains to be had...
