The 4.3 is an inefficient engine as it is. It's saving grace is that it's torquey enough to move decent amounts of weight. But, when you add weight and rolling resistance, it's efficiency is greatly affected and it struggles. I had a '98 standard cab 4.3/5-speed. With 140,000 miles and bone stock, I managed 23MPG mixed. After a few months of ownership (and ZERO traction on wet roads), I changed the stock wheels with 205/75-15s for the stocks off of my Xtreme with 235/60-16 (may have been 65-series, I don't recall exactly). The wet traction was vastly improved, but I never saw north of 19MPG again. Your Blazer came stock with 235s and it also looks like your tires are a smaller diameter than stock. This means your Blazer is "traveling further" for a given distance. For every one actual mile you drive, the Blazer is traveling 1.xx mile. The speedometer will also read faster than what you are actually moving. Disregarding the speedometer and just going with the flow of traffic, you'll be giving it more throttle to keep up at highway speeds. So now the engine is turning more RPMs in addition to the steamroller tires. As a third strike, I'm sure the Blazer sat fairly level, if not slightly sagging in the rear on it's 21-year-old leaf springs. Adding the relatively small weight of the subs and enclosure could make it sit even more saggy in the rear. I can't ascertain from your pics. This greatly affects the aerodynamics because now the nose is higher, allowing all that air at highway speeds to go straight to that very non-aerodynamic underside and act as a drag chute.
If you don't need super wide tires, stick with the factory overall dimensions. Lower the front or, preferably, the front AND rear but keep the back about 1" higher. I wouldn't be so concerned about the relatively minimal weight from the sub system once you have the Blazer sitting corectly even with them in the back.
Oh- and make sure all of your standard maintenance items are up to par: plugs, wires, distributor cap and rotor, fuel filter, fuel pressure, no SES light, etc. If you get bored and want to do a simple upgrade to increase efficiency and free up some power, trash the clutch fan for an electric fan. One from a mid-90s V-6 Taurus fits and works great even on it's low-speed. This is what I used in 3 different S-series trucks. There are others that fit and work just as well and pull less power. To address the current draw, I swapped my stock 105-amp alternator with a stock 145-amp one from an '03 Escalade. It was a direct bolt-in and only required a slightly longer belt. I also used a Flex-A-Lite VSC to control the fan. It starts the fan at 60% power and ramps it up as needed. Running the Taurus fan on it's low-speed side, I don't recall it ever being sped up much more than that initial 60% speed to keep the coolant at 210 or less, even when idling in traffic in nearly-100-degree heat with the A/C on MAX. I free-er flowing muffler (any decent turbo style will do) and a larger Y-pipe (if your stock one is flattened on the lowermost portion) would further increase highway cruising power. Don't fall victim to the air intake gimmicks. The stock one flows plenty, it just needs a better seal to from the engine compartment to the outside air. My stock one had a 3/4" gap where the intake funnel met the hole in the fender. Adding a little bit of foam weatherstripping to close this gap dropped my IAC temps from 100 degrees+ to just a few degrees above ambient.