When I upgraded three of my sites to WordPress 2.6, two of the installations went smoothly and without any problems, but for some reason I couldn't log into my primary weblog site after the upgrade. Whenever I entered my user credentials, I wasn't told that my username or password was incorrect, it just told me to try logging in again.
My first instinct was to clear my browser cache which thankfully in the case solved the problem, though it did give me quite a scare. If you still can't log in, there's a question dedicated to the problem over on WordPress.org; apparently many, many other people are having more serious problems.
It's funny how my opinion of WordPress has steadily been on the decline since the 1.x days… my own biases against PHP (security, version hell, terrible international character set support, lack of proper OOP) aside. It's a shame, because WordPress still has by far the slickest user interface for posting, even if they did take a step backwards in 2.5. The new word count feature is nice though.