I just ran the my first set of WordPress 2.5 upgrades.
The first upgrade was to a very small blog with only 2 plugins, the second was to a larger blog that had several plugins installed. Both upgrades went smooth as silk.
The WordPress 2.5 dashboard and layout are totally different from anything WordPress has released before and it will take some getting used to. I did use the upgrade automatically option on a couple of the plugins and everything worked as expected.
One new feature I really like is the Tag management. As an example I had a tag that should have had a word capitalized that was not. I was able to modify the tag display with a couple clicks and then verify that it was corrected in my tag cloud.
So far WordPress 2.5 looks great and I will follow up with more data as I upgrade the rest of my blogs.