Upright is much more comfortable (
if the bike is
designed for it!) but IME is slower.
The prime example of this presently (in the USA) is the RANS crank-forward bikes, such as the Fusion:
http://www.ransbikes.com/Fusion10.htm
I have had one a few years now.
It's much more comfortable than any regular bike, but it also feels quite a bit slower too (feels like more aero drag). For a lot of casual riders, that doesn't matter much though. The custom seat doesn't require padded shorts, and there's much less hand pressure and neck strain. If you want better comfort but don't want a recumbent, test-ride one of the RANS bikes.
I would also opine that any "upright" bike that still uses a regular bicycle saddle is a waste of your time. The regular bicycle-style saddle is the source of most people's pain complaints. Until you get rid of that, you're still going to have the same butt-pain problems.
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