I have been pleased with mine, I have owned it and a 03 Duramax, and honestly, unless you are doing severely heavy towing on a regular basis, the Duramax is a luxury more than a necessity.
My 6.0 (before it was lifted) did just fine on 285/75R16s with the 4.10s. I managed 16mpg best on the rural highways around here 55-60mph all the time. Highway mileage would usually drop to ~14mpg, as it didn't like the 70-80mph with the 4.10s. City mileage when I was in college in Raleigh, was more like 11-12mpg.
I bought the truck with 65k miles, it had a gooseneck hitch, and reportedly the truck was used ONLY for towing a horse trailer around to rodeos for a team roper, it wasn't a daily driver. I drove it and everything felt nice and tight and smooth, so I bought it. I towed a 35ft 5th wheel camper for a while with it, mostly in the mountains. I managed 10mpg going up 40 through the mountains and 11mpg coming back, pulled like a dream, I was able to maintain the speed of traffic with no issues. Even after it was lifted on 37s (with 5.13s) I maintained 10mpg pulling my CCLB Duramax 150mi home from Raleigh when the injectors went out.
I should note that all of this driving was done with a few mods. Within the first month of ownership the truck had 285s, magnaflow exhaust, and EFIlive tuning. I will say a custom tune is the single best thing you can do for the 6.0. (Superchips/Hypertech etc, need not apply, waste of money). The difference was night and day, and mileage seemed to go up 1-2mpg, although I had only had the truck a few weeks. LQ4s can consistently see 40-50rwhp gains from a tune only due to how conservatively they are tuned from GM. I had the tune, torque management 0% on normal, and 50% on tow/haul, and shift points raised. (torque management retards the ignition just before shifting to save wear and tear on the transmission), 70k miles later, I have had no issues with the 4l80E, although I do run a larger auxiliary cooler than stock.
Really, I see nothing outstanding to look out for on these trucks other than the normal drive it, feel if everything is tight, check oil, smell transmission fluid, etc.
Pitman and Idler arms are normal to go out every 70k or so, faster if on bigger tires, those are easy to swap out, there is a kit out there to put them in double shear and end any replacement, I have had 50k miles on 37-38s with no more issues with those parts now.
Hubs are common wear items, 50-70k miles, again easy 20 minutes to replace.
Driver side front axle seals commonly leak, especially on a truck that has been cranked for larger tires, easy fix, axle simply slides out.
Knock sensors as mentioned are an issue, and are not bad to swap out just takes a few hours. If they are bad, it will kill your fuel mileage because the ignition will be retarded at all times (CEL will be on). If they are bad, it's because either someone used it as a mud truck, or someone washed the engine bay with a hose. GM TSB for knock sensors specifically says do not clean engine bay
Mine went out 2 weeks after I detailed the engine bay, I didn't even use a hose, just a spray bottle. They are located in the lifter valley and water gets trapped there.
Google GM Piston Slap, and read up on it. It is more of an annoyance than anything, sounds like ticking lifters. My truck will do it if I let it sit a few weeks, then will stop after a few minutes. My father in law's 5.3 does it ALL the time, and has for years. My brother's truck did it, and it was still going strong at 280k miles when he sold it.
The fix for this is easy though, if you catch it before it rubs through. I have been meaning to do the fix for mine, but 135k mi and no issues so far.
The speedo(and other gauges) going out was common for 03-07classic models, 01-02 did not have this issue. Many of these were fixed under warranty with updated clusters or stepper motors. If it happens to go out afterwards, the stepper motor replacement is pretty easy.
