Some things are sort of OK, some are amazingly irritating.
The tech tree (as has been mentioned) is a nightmare. You can't zoom out, or if you do its useless. To see what everything does is painful. Initially I spent most of my time trying to figure out what to research.
The city screen took me ages to fathom. It is sort of OK when you are used to it. Why doesn't Esc get me out of it, though? The building list is too expanded and you are forced to scroll a lot, which is a pain.
The alert icons are a mess. Some are coloured, some are not. What is that about? I hate the 'there is an enemy near your city' alert that is small and monochrome. I miss that all the time. Also, some fade in and out of colour, but there is no rhyme or reason to which that I can see.
Still with the damned irritating "let's declare war on ..." dialog that refuses to allow me to see any details of the players. How the hell do I know who is who? Maybe I'll get used to the names, but for newbies (to BE) it is useless.
Unit upgrades and names. I am almost completely lost. All those fancy upgrades (and I like the way it works, just not the damned UI, which is this thread) are converted into meaningless (to BE newbies) names. I have to look at the whole upgrade list to figure out that unit I allowed an extra tile range if it has not moved. The name is meaningless. Which brings me to ...
The Civilopaedia and the upgrade dialogs don't keep their place! If I go back to the game to check what I was doing before opening it, and go back, the dialog is back to the start. That is as annoying as my mother-in-law.
As has been mentioned elsewhere, the trade route selection, as well as being constant, is annoying (also a bit like the mother-in-law, really). The 'previous route' mention is almost impossible to see easily. It should be at the top or in a different colour. The list also cannot be sorted as you can in Civ 5.
How hard is it to see what the turns to finish a build is? I have no idea why that is not better. Actually. I'm not a fan of the transparent city title at all.
Victory ranking is much, much better! I can now see clearly where I stand, and how close others are to winning (ie who needs a kick in the wossnames right sharpish).
Quests dialog is a bit odd. Also, the 'show failed quests' checkbox does the opposite.
Right-click on unit pics (bottom-right of the screen when selected) does not take to the Civilopaedia entry like Civ 5 does.
Esc does not always dismiss things, making me hunt for the randomly-placed close button/word. That was true in Civ 5 too, but seems worse in this one.
Overall, not very impressed, and most of this could/would/should have been picked up in User Acceptance Testing in my world. It looks like that is what we are doing now, just like with Microsoft products.