Most "C"s are essentially vans with a box on/around the cab. The Econoline series has been around so long, most major show-stopper bugs are pretty much gone. This doesn't mean there are not lemons, but all and all, they are pretty reliable. Sprinters are similar. If you have a T1N Sprinter, you get the metal carb resonator. Both Sprinters, you get a transmission cooler added, if it isn't there already.
There are two things which kill Cs:
1: Water damage. A lot of older Cs have windows in the cabover, and seams on the corners. This almost guarantees water damage and major rot after a few years. The only real way to deal with that is to buy a "C" that either is fiberglass (Born Free, Coach House), or a "C" that covers the seams with fiberglass caps, so they are not directly facing incoming water coming in at 80+ mph (60mph of rig + 20mph or so of the wind) when going on the road.
Of course, it can't hurt to get a rig with a fiberglass roof. That way, a twig scratching it undetected won't cause major water damage down the line.
2: Neglect. I've seen lots of rigs on CL and other used sites with the other touting "2002 blah-blah, Just 10 hours on the generator!". I would rather have a rig with a generator with 1000 hours on it, that has been maintained to Onan's schedule than one with 2 hours on it that has just sat there, factory oil still in the pan, windings corroded into something only copper thieves would want to grab, and a carb that is completely inoperable due to varnish. Similar with engines. A 10 year old coach still sitting in its factory engine oil at 5000 miles is a lot scarier to me than one that has seen 100k miles on it, but has had the upkeep guide followed to the letter.
Neglect also invites other problems. If mice infest a rig, the entire thing might have to be totaled, and possibly torched due to hantavirus or other rodent-borne diseases. Undetected rust can also be a vehicle-killer. Of course, neglect can end up causing water damage which would have been detectable and fixable to turn a complete rig into scrap.