Look at the V8 swap article in the information section of the main luvtruck.com site. A 4.3 shares a lot of characteristics with a V8 so that should give you some idea of what you are getting into. Just about any swap will require some of the same steps.
The 4WD system has a lot of "depends" in the answer. I don't know which side the front drive line comes out on the S10, but that is an issue only if you are keeping the stock LUV front axle. LUVs have the front diff on the left, but some trucks have it more to the right. You need a straight line from the transfer case front output to the differential. If you put a solid axle under the front end, you just need to pick something the matches the engine and transfer case you are dealing with. So it depends a lot on what else you are doing with the truck. Anything will fit if you do enough fabrication work, but some things fit with a lot less work than others. I think I'd do some looking at 4.3L swaps that people are doing on other rigs, especially Isuzu Troopers/Amigos/Rodeos and see what barriers they found and how they overcame them.
http://www.4x4wire.com is a good place to look for Isuzu info, especially the TrailTalk BBS forums there.