In the last 2 years I've changed my bike from a torture rack, into a very comfortable ride. The night before last I rode it over 40 miles in one sitting like it was nothing. This is how I did it.
Here's before, and after views to help explain the changes.
Get rid of rigid forks. I've tried rigid, cheapy suspension forks, and springers. The springers are by far the most comfortable.
2", and wider tires are best
A low seat height is important. I got my seat height so low that when sitting with both feet flat on the ground, I have to bend my knees. This was achieved not only by lowering the seat all the way down, but also installing bent fork springers, which lower the front of your bike 3". For motorized bicycles that are only going to be street ridden, most bicycles are too tall.
A spring seat is better than a gel seat without springs, for long rides, but you may not think so at first. Give it about 10 or 20 miles, before you decide. My seat is a very inexpensive, walmart spring seat, common on many MBs.
Change your handle bars. It's essential to have comfortable handle bars. Exactly what's comfortable is going to be different for everybody. I don't like leaning on my wrists, so I like tall bars that allow me to ride sitting up doggie style. Soft grips are nice too, especially the kind with broad flat surfaces for your palms.
The best way to control vibration is to lower rpm. You can't expect not to have a ton of vibration if you're cruising at 7000+ rpm. Gear your bike to cruise at no more than 6000 rpm. 5800 is even better. My bike is geared such that 5800 is equal to 30 mph. This gives me enough reserve, to go 35 mph for short bursts if I feel the need, because of traffic situations. For extremely long rides I might cruise at 26 mph. That works out to about 5000 rpm. Right in the torque sweet spot of a stock motor. That's where you'll get the best gas mileage, and throttle response, and vibration is almost nonexistent.
One last thing I reccomend is good brakes. It's hard to be truely comfortable if you're always worried about getting run over.
As far as comfort is concerned, I give my bike a 10 out of 10.