My wife has a 2001 2500HD with the 6.0/4L80E/4.10. It has impressed me.
I have seen as high as 16mpg highway with it. Towing is typically in the 10mpg range. Around town is usually in the 11~12 range.
My oldest son has a 2005 just like the wife's. He works his pretty much the same as we work the wife's.
Both trucks have been rock solid.
As far as comparing it to a 5.3...... I've only towed with a 5.3 once. It did a fine job but I don't think I have towed with it enough to compare the two fairly.
Now if you want to talk about my truck, it is the beast, it has the 8.1L. :B