I am considering updating, but the server has an uptime of 100% over the last 12 months... although hasn't been updated for the last 12 months, except for basic DirectAdmin and OS-updates.

The server is hardened, but the software is getting outdated. Can anybody help me find a howto for updating CentOS 4.6 to CentOS 5.3?

And can I expect problems with DirectAdmin not functioning anymore afterwards?

I would look at the packages that you will gain and how badly you need those features. When you jump major revisions(4.x to 5.X) it is best to do a clean install, in my opinion that is a lot of work for minimal added features. The other thing to consider is that RHEL/Centos 6 is due out before too long (MAYBE October? probably depends on how F11 works out).

I have no need for additional features. Security is what's currently important to me.

Doing a clean install is not an option. I consider having to use a 2nd server and copy backups on a new DirectAdmin server as a bad solution, as we have spent quite a few hours to optimize the server and make mocifications.

As far as security there is very little to worry about. RHEL/Centos back patches all their packages to be as secure as current packages.

A lot of your optimizations and modifications will probably not function properly when you jump major revisions (4.x to 5.x). This is why RHEL/Centos has a five year(plus) support life. One can "dial in" the box and just leave it set for years without having to do much more than run regular updates. The bad side of that is when you jump major revisions the OS and related packages have changed significantly enough that you essentially have to start over and "dial in" the new OS from scratch.