At the risk of being objected to, let me say that for starters, a cruiser is probably not your best choice for long distance touring, especially 2-up. It really wasn't meant to be that. There are bikes made specifically for that purpose, such as the Gold Wing, the HD Ultra, Kawasaki Voyager, Victory Vision or Cross Country Tour and the BMW D1600GTL. These are all smooth, some more so than others.
But like Romans said, what you choose to ride depends on what kind of riding you prefer. You certainly don't want a Gold Wing if all you do is run around town, for example. Any bike can be a touring bike--all you have to do is ride it to wherever you want to go--but some are purpose built for it and do a much better job at it.
V Twin engines are not as smooth as inline or horizontally opposed engines because of their inherent imbalance. Some inline 4's are quite buzzy, as well. One well-known culprit is the old Kawasaki Concours 1000. Good bike, but a very buzzy engine. Tinkering with timing and carb balancing can smooth it out some, but never totally removing it. On the other hand, HD has taken a well known paint shaker engine and rubber mounted it in the Road King and Electra Glide series and made them dead smooth at speed. So it can be done.
In the end, only you can decide what kind of riding you will do, then choose the right bike for the job. Good luck and keep us posted.
I don't know, I rode my 1500 classic on several long trips (and I mean LONG- North Idaho to San Diego and back 3 times, a few trips to the Oregon Coast, up to Glacier and Jasper/Banff, the Yellowstone/Jackson/Hell's Canyon loop, etc) and found it to be reliable, comfortable, and easy to ride all day long. More than enough power, plenty fast, nimble enough for mountain roads. I'm a big boy, too (6-4 and 270) and it carried me, my wife, and all our gear just fine.
People have been touring on Harleys for 75 years or more. The design of the 1500 classic is no different the design of the HD touring bikes, except I don't have a trunk or a fairing. It's still a V-Twin, just like a Road King or an Ultra Classic, except I have a shaft drive and a watercooled engine, two pluses for touring.
I suppose the difference between my bike and a Goldwing would be the difference between touring with a Toyota Camry and a Cadillac. Both are more than adequate for the job; the question is how much luxury do you need?