2.73's to 3.42's
 

I was wondering if I need to change the tune if I swapped gears out. I'm not worried about the speedometer being out of whack, just wondering if the transmission will act differently? Any suggestions?

This is going on a 01 C5 Vette with a 4L60 trans.

If you really don't care about the speedometer, then you don't need a tune.
However, when you do get tired of the 20% speedometer error, find someone with e.g. HP Tuners, pay him $100 for the "credits" to tune your car and it takes 5 minutes. HP Tuners lets you change the rear ratio and automatically change the transmission shift tables MPH by the same percentage.

Thanks for the info!