I feel like a comfortable ride is more about where your seat, pedals, and handlebars are in relation to each other. The fact that there's more seatpost on a small-wheeled bike never seemed to be an issue with me. Although I do think smaller wheels may let you feel the bumps better, but I only find that to be an issue when I'm on gravel.

I just took a several day trip on my Raleigh Twenty. Longest day was about 70 miles. There were some saddle sores associated with that trip, but the same is true of long days on my full-sized touring bike. Still, all things being equal, my Long Haul Trucker is a more comfortable ride. But my Raleigh Twenty did just fine, and had the added bonus of packing up into a suitcase at the beginning and end of my trip.