You may want to read through the thread "Ho 48re owners, any regrets?" for some discussion on this question. I bought the 48re, and really like it. It is under the powertrain warranty. My reasons were:
I drove the 6 speed and the 47re before I ordered, but the decision was relatively easy for me. The reasons were:
1. The 6 speed is a lot of shifting around town. It is a tight pattern, but not hard to hit shifts. The number of shifts was an inconvenience I did not feel I needed or wanted for my use of the truck.
2. The tow rating of the 48re is the same as the 6 speed. Not almost, it is the same. I ordered the 48re without driving it, based on the information on the TDR about how it was built. Related to that, information here indicated it was expected to be e-brake compatable and people have already put on Jake and Pac Brakes, and others I assume, with very good results. I think testing is still going on, but approval for an e-brake without warranty issues, may be only a few days or weeks away.
3. I am not hauling max loads, so 4 speed vs 6 speed will not be any problem for me. When pulling the 5k trailer I have, it has had no trouble maintaining 60 MPH up a 5-6% grade, and it feels like it will take a steeper grade without a downshift. I am passing a lot of passenger cars with no trailer at all going up that hill.
4. I am not buying the theory that for highway driving the 6 speed is better. In fact, in town the 6 speed is more trouble; and on the highway once you shift up to 6th, the auto and the stick drive just the same. Any difference is on hills, where the stick gives you more choices about what gear to be in for the climb. As I said, the auto in 3rd can really climb with the load I am pulling, so the additional options seem to be unnecessary for me.
5. Probably most important is that this is a retirement truck, and my wife and I will both be driving it while we are traveling. She can drive a stick fine. For both of us, the 6 speed with the clutch would be added to the trailer and the mirrors and the length of the combination; all complications that add to the distractions while driving. Eliminating the clutch and shfting just makes it a little simpler, and keeps more attention on the road instead of what we are doing in the cab. For that reason, it is probably a little safer.
All of that said, if you are going to pull max loads, mostly on highways with a lot of hills, the 6 speed is probably better for that. That just does not describe me.