In my experience, the pavement on I-76 is typically in better condition than the pavement on I-80. (Probably because it's a toll road.)

I-80 seems to be home to a LOT of semi trucks, which isn't to say I-76 doesn't have lots of trucks too, but in my experience I-80 has a LOT more.

You're gonna have to go over some mountains on either one, so brace for that. It's just reality that there are mountains between here and there.

I-80 is a lot straighter than I-76, so may be less "crazy" by some metric.

I-76 is gonna cost you more in tolls than I-80 will.

I generally prefer I-76, but that's because I've driven it so much that I know it like the back of my hand.

As someone else pointed out, I-76 will very likely be faster.

If you like to drive in excess of the speed limit, my sense is that you're more likely to get away with it for longer on I-76, but this is just a gut feeling, and not really data-driven. (I-80 has lots of long, straight, flat sections that look fun to speed on, but make it much easier for the cops to radar/laser you.)

Edit to Add: Oh yeah... if you're planning to get to I-80 by taking PA-22, be forewarned: During the day it is its own circle of hell. There's gotta be 3 dozen stop lights between Monroeville and Hollidaysburg on PA-22. I hate that road and avoid it at all costs. If you're dedicated to taking I-80, I'd recommend just taking I-79 North over PA-22, but that will take even longer.