Scroll Preferences
The biggest problem I've found with Lion so far is with the scroll preferences - I have a Macbook Pro, and I use a Magic mouse with it. I was using the mouse when I installed Lion, and the scroll inverted. I went in to preferences, and disabled natural scroll, restoring the way I expect a mouse to work. Then I discovered that all the gestures on the trackpad were now inverted.
It appears that natural scrolling is a system wide option, rather than being device specific. Mice and Trackpads are not the same Apple. People use them differently and now that particular scrolling option locks them together.
I'd like to see this become device specific, and I'd also like to see the scroll reversal configurable on a per axis basis too.
I guess I'd better get used to either fucked up scrolls on one device or having sys prefs open all the time :(