I totally agree with Jeff about improvements to the editor. It has come a long way, but since it's core to what a lot of people do with WordPress, it should always be an area of improvement focus. This new version sounds great in that regard.

I'd really like to see *major* improvements to the comment system. Again, it's core to what many do with WordPress (i.e.: blogs), and comments are crucial to blogs. And, not to offend anyone (who has probably worked hard on it) if possible, but the current comment system needs a lot of work. I'm always a bit amazed we're this many years into WordPress and it doesn't have better core functionality in that regard. (Unfortunately, I'm probably headed to DIsqus, as I'm just sick of waiting, but it is something that so many need badly.)

And, I agree with Marcus about backup and core. Anything that is a necessity should be in core, at least in some basic usable form.