1) Focus on ease of developer support and application stability. QUIT releasing a "new" operating system every 4 to 7 years and start releasing "Windows Business" 2.0, 3.0, 4.0, etc. This way developers can easily tell the end user "To run this version of our application you must be running 'Windows Business' 3.0 or greater". Then charge $99 for users of "Windows Business" to upgrade from 2.0 to 3.0. What changes in this upgrade? Oh, not much, a few minor feature improvements and new development libraries.
2) Focus on management. Part of what I mentioned in the ease of developer support falls into the ease of management. (EG: "Dear IT, We need 'Windows Business' 3.0 to run our applications.") Now to focus on IT. Sure, Windows 2000, XP, Vista, and so on are all "easy" to manage. Gobs of GPOs and 3rd party tools, but come on! I want to see REAL management. How about licensing, for example. I have yet to see an obviously easy way for IT to audit their licensing. There are a lot of solutions for it and they all do it their own way, but if MS wants to keep people legal, you'd think Windows Server would have a licensing management, auditing, and tracking system that far surpasses what we have now. I digress. Every aspect of "Windows Business" should be manageable without the need for 3rd party utilities. I could go on talking about management needs for days.
3) Users need a simple environment to work in. This is really a mixed topic for both ease of management and ease for the end user. Windows is already customizable and you can lock down the user environment to specific apps and profiles, but this isn't good enough. It's a PITA to get things just the way you want them. We really need to be able to easily make an over-the-top application specific end user environment that really completes the entire package. Remember, the computer at work is a tool to do work, not a "computer" in the typical end user sense of thinking.
To finalize, MS needs to take the market position and technology they already have and make it work for the people, instead of making the people work around the technology.