the worst thing I can think of other than obvious rod through the block, engine smoking, or rod knocking, is the bad lifter worn cam issue some of the people who own the vortecs experience.
I had never heard of this before until my wife's 4.8l 144k mile engine began making a chirping/ticking sound just after Christmas. More of a chirp than a tick. EVERYONE, myself and 6 different mechanics with a multitude of experience, thought the exact same thing at first. It has a bad pulley bearing(it really sounds like a chirping noise/bad roller bearing).
Mine kind of sounded like this but not as loudly pronounced
https://www.youtube.com/watch?v=3J_DnWMYa7g
sound went away at 1500 rpms and was not present on cold days until engine warmed up.
Basically that sound is $600 in parts doing it yourself.
$1100 for a local shop(not dealer) to do it if the cam does not need to be replaced
$1600 if the cam is bad too.
So basically you might as well buy a crate engine or a salvage engine and swap it out.
I'm sure I'm going to catch some flak over the prices above but that is what my local area (Houston) demands.
Cam-$250 stock
set of roller lifters $120
top end gasket set $200 (you could save $60 here and go with cheaper gaskets)
cam bearings $25
Of course since your there you may as well replace oil pump $50, and timing chain set $90, lower gasket set $94 (oil pan needs to come off to replace oil pump/ clean oil pick up screen)
This is the number one thing I would be concerned with. The noise does not have to be as pronounced as in that video link. It seriously sounds like a bad tensioner bearing. I originally pulled the belts, found a bad a/c tensioner and really thought I had the issue resolved. Until I started the engine without the belts and the noise was still there.
I have heard of many of these engines going 200k+ miles and never having this issue. Then there are some I have heard of that get it at as low as 80k.
Before people go there, We bought the Tahoe at 20k miles, had oil changed every 3k miles(I can think of once where it got to 5k before the change) under valve cover slight yellow discoloration and absolutely no sludge to be found. This engine has not been abused in any way.
Also just prior to noise, I started getting a check engine light, I pulled some codes but off the top of my head I can't remember the numbers. One was a possible bad catalytic converter, other was a random misfire which only occurred the day I actually began working on it.
After engine swap, no codes have appeared.
Somehow I went from trying to tell you what to look for, to telling my story(must have hit a sore spot) anyway I apologize for it but I'm not erasing all that typing.