Sophisticated engines have sophisticated problems, particularly when they start accumulating years of use. The S-10 and GMC Sonoma's ignition systems use a variety of sensors, triggering mechanisms and coils to keep everything running smoothly; every single one of those components, however, is a possible point of failure. Fortunately, symptoms of failure remain fairly consistent, so finding the failure is just a matter of knowing what to look for.
S-10 Engine Basics
The 1999 S-10 came with two different engines choices: the 2200 Vortec four-cylinder and the 4.3-liter V-6. In terms of ignition and fuel injection, these engines are on entirely different planets. The 4.3-liter V-6 is a six-cylinder evolution of Chevrolet's 350 small-block, which hearkens back to the 1950s; it uses a sort of retrofit EFI system and a traditional distributor, a remnant of its days as a carbureted super-beast. The 2200 is a more modern entity, designed for electronic ignition from the outset. As such, it uses a host of sensors, a coil pack and a computer to ignite the spark plugs.
Electrical conductivity decreases with heat, and an inefficient conductor produces more heat. This leads to a cascade effect of thermal buildup that starts when you fire up the engine and continues until heat in the coil eventually overwhelms its ability to transfer energy. The 4.3-liter's distributor uses a single coil, just like its 350 ancestor, so a coil failure will result in multiple misfires, and ultimately in engine stalling. The 2200's multiple coil packs are unlikely to fail simultaneously, so a coil failure will typically result in a single-cylinder misfire that will likely get worse the longer the engine runs.
Triggering System Failures
While the 4.3-liter does use a distributor, it also uses a crankshaft and camshaft position sensor, just like the 2200. The CPS is a magnetic sensor, functionally identical to an old crank-trigger system; it works like a super-accurate tachometer that tells the computer exactly where the crankshaft and camshaft are positioned in their rotations. The 2200 uses its CPS sensors to determine every aspect of timing and triggering, but the 4.3-liter's computer uses them primarily to adjust timing and control the fuel injectors. The computer sends its altered signal to an igniter, which acts as a relay to trigger the ignition coil. Triggering system failures will typically result in random misfires, leading up to total system failure, but a CPS failure in either engine will disrupt the fuel-injection system, as well.
Plug Wire Failure
Unlike later coil-on-plug motors, both of the engines of this vintage use spark plug wires. Spark plug wires, like coils, both decrease in efficiency with heat and build more heat with increased inefficiency. Eventually, the metal core inside the plug wire will degrade to the point that it the electricity jumps through the insulation and to the nearest ground or adjacent plug wire. This is particularly true if the insulation itself is dry, cracked and worn. Spark plug wire failures will almost always result in a single-cylinder misfire that may or may not occur randomly; it all depends on the type of failure. Additionally, cross-wire arcing may prematurely ignite the mixture in and adjacent cylinder, which can result in knocks or pings. The simplest way to diagnose plug wire failure is to start your engine, turn out the lights and watch for fireworks under your hood.