Better user interfaces.
Today’s user interfaces still suck. And I don't mean in small ways but in large, fundamental ways. I can't help but to notice that even the best programs still have interfaces that are either extremely complex or that require a lot of abstract thinking in other ways, and that just don't approach the ease of conventional, non-software tools.
Granted, this is due to the fact that software allows to do so much more than conventional tools. That's no reason to accept the status quo though. Additionally, most software is simply not well done.
In general, applications still lack a certain “just works” feeling are too much oriented by what can be done, rather than what should be done. One point that has been raised time and again, and that is still not solved, is the point of saving. Applications crash, destroying hours of work. I have the habit of pressing Ctrl+S every few seconds (of course, this no longer works in web applications). Why do I have to do this? It's mind-numbingly stupid. This is clearly a task for automation. Of course, the application also has to save a diff for every modification I make (basically an infinite undo list) in case I make an error.
Solving this probem isn't even actually hard. It would just be hard to implement it in every application since there is no good API to do this. Programming tools and libraries have to improve significantly before allowing an effortless implementation of such effords across all platforms and programs, for all file formats with arbitrary backup storage and no required user interaction. But it is a necessary step before we finally start writing “good” applications instead of merely adequate ones.
I believe that Apple currently approximates the “just works” feeling best in some regards. Take for example their newest version of iPhoto which features a face recognition that automatically groups photos by people appearing in them. That is a classical task that the user does not want to do manually and doesn't understand why the computer doesn't do it automatically. And even iPhoto is still a very long way from a good UI, since said feature still requires ultimate confirmation by the user (for each photo!), since the face recognition engine isn't perfect.