I have a 2015 Sierra 5.3 with the 6l80 that has 249,000 miles currently. The engine has been mostly flawless. I changed the plugs out of guilt at around 200,000.
I am on my 3rd transmission, though. The first died at 122,000, and the dealer helped me on the warranty and covered half of the replacement cost and I got another 100,000 mile warranty. That one died with 103,000 miles on it and I decided to get it rebuilt with better parts, a 40K cooler and other mods to make it live. (fingers crossed)
On the second trans, I did get the tune changed but I did not remove the thermostat. I did not know that they had them until it was too late. The rebuild does not have the thermostat. I also upgraded the convertor and had another tune put in. So far so good but I don't drive as much as I used to so it only has about 30,000 miles on it in the last 18 months.
Regarding the engine, I did regular oil changes with full synthetic oil at 7500 to 10,000 miles and have been fortunate to not have had issues with the lifters. I did turn the AFM off at about 75,000 miles and then had the whole combo retuned when the trans was replaced.
I had to change the radiator due to it cracking, so while we were there we also replaced the water pump, but it did not need it.
It has been solid, other than the transmission.
A coworker bought a 2016 and the trans went out about 120,000 miles, too. He is not into modifications, so he sold it once he got it replaced. I tried to get him to get it updated with a tune and removing the thermostat but that is just not his gig.