There were a couple of stretches on Mac 'n' Cheese where I really would have liked to have bigger tires. The long stretch of road with expansion joints before the lake control on day 3 being the prime example. I'm pretty sure I got nerve damage from that road. Also, I thought I was going to get pinch flats while riding in downtown Green Bay.
I switched from 25mm tires for good when I got a pinch flat in the dark in the rain just after the start of a 400k. I had already ridden a series on 38mm tires, and not worrying too much about not seeing a pothole was nice. And I don't think they slowed me down much.