The Nissan Path

Re: 2011 LE V6

1. Is there any measurable difference in either tire wear or fuel economy running 2WD v 4WD?

2. What did you upgrade your radio to in order to get a decent hands-free solution? (The stock unit is horrible against today's standards.)

Since you have an LE, you are referring to the AUTO mode transfer case and I would have to assume you mean 2WD versus AUTO mode rather than versus 4WD, which you would only use during conditions that require it. In AUTO mode, you are still driving in 2WD under most driving conditions. The front wheels are only supplied power during conditions that require it and can be applied proportionally via its wet clutch.
If that's the case, I haven't noticed any difference in mileage between 2WD and AUTO mode. It's also not going to matter as far as tire wear. Personally, I just leave mine in AUTO mode almost all of the time. The only time when it's not in AUTO mode is when I encounter several inches of snow and I switch it into 4WD-HI.