Get 15+ mpg? Possible but you gotta trim it just right.
This comes from getting more out of my old rover.
1st off, tires. I drop about 3 mpg going from 235/85/16 tires to 34x9.5 TSLs. I end up losing about 75 miles of range which sucks a lot. If you want to run 40" knobbys then no, you ain't getting 15 mpg. However if you keep it under a reasonable 33" and not 15" wide, then you are closer. Sounds like you want a street truck so going with a more reasonable size like a 265/75/16 or something like that will rock. Also on that note, reduce your tire/wheel package weight. A set of nice light street tires on some factory like alloys will be better than heavy carcass tires with dual beadlocks.
2nd, a good engine. Crappy underpowered engines don't do crap in the power nor MPG department. When I finally got my engine up to snuff, I noticed it held on the hills better, I wasn't using as much throttle, and I got better mpg. So yeah, if you are doing an engine replacement, get like, 400 hp. Also on that note, you might as well get a complete Chevy Gen 3 engine (like an LQ9) to throw in there. Good power, cheap, plentiful. I would say get a Gen 4 + 6 speed auto trans but you've already veto'd that. However a Gen 4 6.2 engine with the engine management (aka, cylinder delete) would help you out a lot on the highway.
Feel free to open up the exhaust and put a LS intake manifold on it but don't be going and throwing a cam and giant injectors in it and getting it tuned to the moon. Think efficiency and you'll get mpg and power.
If you put a carb on it, you deserve all the crappy MPG you get.
Be careful about putting a non-truck engine into a truck. They'll build their power at much higher RPMs. This is crap for a truck application and highway cruising. Also be careful of a LS1/2/3 used. That means it came out of a Camaro or Corvette...that was probably wrecked...guess what aluminum blocks don't like...
For gearing, set it up so you are using that nice low end torque. Something like an LQ9 will give you mighty fine power at 1500 rpm. So you can use that for highway cruising but not blowing up the gas tank. You said you want a manual trans, I'd look to see if a G56 would mate up to a Chevy engine. I did some research and you can get a nice new unit for like, $2k (if memory serves). This unit is great because you aren't going to be torque loading it (its for a diesel application so it should be able to handle a gasser without much issue) and its light. Same with a Gen 3 iron block, they are actually pretty lightweight and you'll probably be shedding weight by upgrading. On top of that, these old trucks are actually pretty light. Just think on the weight savings and it'll go a long way despite the fact the truck isn't aerodynamic worth a crap.
You'd probably end up running a 3.73 diff gear or something like that. This is alright assuming you start off with a transmission with a ~4:1 1st gear and your run of the mill stock chain driven transfer case. If you absolutely gotta have the crawl capability, then get you a 4.3:1 Atlas 2 speed but a chain drive will be great for street and help with your efficiency.
