A problem that has hovered over WPMU like a bad smell for years but which has never been satisfactorily resolved is MULTIPLE DOMAINS. Wave after wave of new user, upon discovering MU, have asked what seems to be a natural question: "How can I give each of my blogs their own domain, but still manage them from one central installation?" and, time after time, they have been told "That isn't what MU is for!".
That is true, MU was always been geared towards large organisations such as universities who want to offer blogs to their students, all under one domain, but that fact has not stopped tens of thousands of users hoping that it might be a solution to the ridiculous problem of having to manage and update multiple installations of WP.
Now that WP and MU are merging, that shining ideal, of using just one installation, is going to occur to even more people and the forums will be awash with desperate pleas for a solution that works. At the moment, they are forced to wade through an endless maze of ancient forum threads and contradictory blog posts, pointing to an array of half-working plugins and core hacks that haven't worked since 2.3.
Rather than continuing to bat these requests into the undergrowth, official multiple domains capability should be added to the core as soon as possible, ideally at the same time as the MU merge. The number of people using WP is increasing but it would also promote growth if it was easier for each user to run multiple WP sites (with the side-benefit that easier upgrading will decrease the number of insecure WP installations).
If Drupal and practically every other CMS can do it, surely WP should be able too?