It can be done....
While I wouldn't argue the infinitely more experienced voices on this forum, I would say there are some perfectly good reasons for trying to go the route you are suggesting.
While I was not the one who built the rig I own, I do know something of its history and it might be a basis for some insight.
Here's a couple of links relating to Brad's tour of Central and South America:
http://www.truckcampermagazine.com/index.php?option=com_content&task=view&id=110&Itemid=34
http://www.lancecampers.com/livingthelancelife/bradchrist.html
Basically, he considered a few types of rigs, but wanted to set something up fast, and relatively cheaply. Converting a 2WD T or W series GMC or F650 would be 20K or more, so he was thinking F550 or GMC4500/5500. Anyway, he spoke to Ford mechanics about spare parts he should bring if he bought an F550 (this was pre-6.4) and it was pages and pages.....when he spoke to GM mechanics, they said some fuel and oil filters and fuses. He didn't even take a spare tire/wheel, just a patch kit (that seems insane, but nonetheless he did it.)
They put 32,000 miles in the course of a one-year trip and had basically no issues at all.
Many of the overlanders (e.g. Dana Hackney) seem to often state that the vast majority of the roads travelled do not require a serious off-road rig....in many cases it is better to do those total backroad exploring in other vehicles and/or with local drivers. YOu see pictures of stock American trucks with stock truck campers on them. You even see pictures of 2WD motorhomes out there 'doing it.' It can be done.
I cannot really comment on relative strengths of axles and transfer cases as I don't have enough experience with that stuff. But I can comment on a few things.
I would agree that a small cab (cabover) with no rear seats would provide the most room leftover for a cabin. However, the cab of a Kodiak/TopKick in the regular cab arrangement is pretty short...shorter than a regular cab pickup I believe and provides awesome views of the street. When I drive a traditional pickup now I can't get over how long the hood is, and how big the blind spot is in front of the bumper. At this point, we were not ready to give up the extended or crew cab (our first choice would have been an extended cab) so in the Kodiak we like the crew cab. It is giant....bigger than a Megacab Dodge inside....but from bumper to rear of cab it is right about the same length as a crew Cab Ford. If you need a big cab, this is a pretty nice option. Note the Eco-Roamer rig that not only has the crew cab, but he extended it furthur to add room for jump seats and computer stations. If you need that cab-room the trade-off may be worth it to you. Our 9 foot flatbed was cut down to a little over 8 feet, to match the standard Ford bed length, which consequently matches the floor of the Lance perfectly with not an inch to spare, and the frame ends (which stick out almost a foot) do not interfere with the Lance as it is far enough below the deck height.
Brad (the guy who setup my rig) drove it from Maryland to Panama and then shipped from there to Lima, Peru from my understanding. If you were going to use it much in the US on interstates and the like, it is nice to be able to set the cruise at 70MPH or more, and be able to cruise comfortably that way. If it is all 3rd world driving.....this may not matter.
What else? Charlie is right, it has a Dana 60 front end (in 06 they went to a 8000lb rating, mine is just 7K and weighs out about 6500 fully loaded) and the rear is an S110 (13,500lb rating; I weigh out at up to 12K+.) So I do not have a lot of 'extra' axle capacity.....no doubt. The newer Duramax versions will require ULSD and may not be suitable for international travel yet...that started in what, 07 model year I think?
If I were buying new, I would get a 5500, not a 4500. Essentially everything is the same, except rear springs...but it does give you 2K more rating on the GVWR.
We love our rig, but no question, it is not as capable off-road as you or others might prefer but it can be used as a chassis successfully.
My own plan is to build a custom box camper to replace our Lance 1191, but make it removable similar to a truck camper. That is an important feature for us. That would then allow us to later consider changing chassis over to something that IS more heavy duty and/or off-road capable such as a T7500 or an International 7300. Or just keep using the Kodiak chassis we have if we end up without complaints. I would like to move it over to super singles and better springs/suspension, as well as a torsion-free chassis mount for the cabin, but those thing would raise the deck enough that I will not do it until AFTER building a custom box that is not so tall. I am already 13'2" and will not raise another inch if I can avoid it!
Here's a few shots of my rig....
This one shows a size comparison with a 1-ton Ford, with a shorter camper...his is a 9'9" I think whereas mine is 11'9"
Plenty of GCVWR for towing:
Using our dirt bike/flatbed trailer for a deck:
Not too bad an approach and departure angle....I've certainly seen worse..
Hope this helps!
BT
PS: As much as I would love to have a rig I could drive to the top of Taylor Pass and camp for a week, I have to face reality that we actually use our camper much more often simply at the end of USFS roads and explore the tough stuff via dirt bikes. For us, this is a much more feasible and successful way to explore the "world" around us....