The MapServer 5.0 plan has some compelling items (feature-level transparency, AGG rendering in particular), but the one thing I'd really like to see is separation of MapServer's cartographic and web application aspects. These are entangled both in the code and in configuration, so it's no small task, but one that would reward the community.
Frankly, making effective maps and administering a web server are skills that rarely go together. Separating cartography from the web application allows changes to be made to the cartographic presentation with greatly reduced risk of breaking the application that serves up the map. The separation would also make it easier to test and deploy maps, even across platforms.
Similarly, separating these concerns would make development of MapServer a bit more sane. Cartographic enhancements would be much less likely to break the web application, and the upcoming changes to accommodate WFS 1.1 and WMS 1.3 (for example) would be much less likely to break the cartographic engine.
Last, but not least: I consider the built-in MapServer web application (mapserv, or mapserv.exe) to be cumbersome, and a bad investment today. The W*S protocols are better implemented in your favorite web programming language. PHP, Python, Ruby, .NET -- all surpass C for working with HTTP requests, strings, and XML. All have better templating. All have better memory management (except perhaps PHP). Back when I was playing ultimate frisbee, we used to heckle our teammates, yelling "Drop the piano!" at the tired guy who couldn't run down the disc. MapServer's built-in, written in C, web application is that piano.