I've had a Hypertech programmer on my 2005 Duramax for over 80K miles now, and have not had an issue. I run it on either stage 2 or 3 for daily use, and only stage 2 when towing. Hypertech indicates it's the only tuner you can safely tow with on any stage, but I only use stage 2 to tow with and am very happy with that.
It's not the most powerful programmer/tuner you can get, but Stage 3 is a real kicker (+87 HP and +173TQ). Stage 2 gives 52 HP and 108TQ. It is an absolute difference in power.
The programmer takes a snapshot of the OEM programming before applying its settings. I can restore the original programming at any time, which I do when getting smogged here in CA, and has always passed. Then I just reprogram to stage 2 or 3.
As far as mileage is concerned, I couldn't tell you (though it's certainly not any worse), but that's not why I got it. Actually, the main reason I got it was because my speedo was off when I changed to larger 285 tires many years ago, and wanted something to adjust the speedo. I went to a race shop and they a Hypertech product to do that, but for not much more I could get the full power tuner included, so I opted for that, and am very glad I did.