Absolutely, there is a difference. Custom files are the only way to go in my opinion.
Research and select a tuner, then have tunes written to your trucks strategy, modifications, and power goals. The generic files can't cover everything out there, there are too many variables to the 6.0L.
Different tunes will have a different feel, so I suggest you take some time to look at them on the ORG here. There's a lot of threads covering the most popular 3, and the differences between turners becomes apparent.