What is your most common discomfort issue?
Fatigue, saddle soreness, neck stiffness.
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The neck issue could be remedied by more upright position. A proper bike fit is the starting point.
Also chances are that there are other saddles that you will find more comfortable than your current one.
As for general fatigue, could be fitness or perhaps the bike is beating you up a bit. Some people simply suffer more from certain qualities of certain bikes. I find my hands take a beating if I ride a very rigid fork - some of the new disc forks are bricks. I am totally unaffected with more typical road forks.
In general to answer your question, there can be a huge difference in how some people will feel between riding a bike that they find very comfortable and one that is less forgiving. I adhere to a couple of basics to maximize comfort as far as the bike goes. 27.2 seatpost with lots showing (so sloping top tube), and stem and handlebar not too stiff.
I don't know how much more comfortable an Emonda would be. Certainly the Domane would be comfortable but they are heavy and the geometry is not for everyone. Even the new SLR is not that light. If I had to choose the ultimate in comfort but still raceable, I would get a Cannondale Synapse Hi Mod. The Black Inc. version with rim brakes would be my pick.
All of this assumes that you have optimized your tire situation which you seem to have done.
When we ride disc brakes the whole deal of braking is just like a leaving a fart. It happens and then it's over. Nothing planned and nothing to get nervous for.