I apologise for my last post on this topic, it probably wasn't very interesting :-)
I've done the Drupal 6 upgrade, and it was relatively painless. Most modules ported smoothly, a few required me to learn how to port modules to Drupal 6, and one I just gave up on.
On the whole, the porting is simple, Druplal.org has a pretty good howto on the topic. A few APIs have changed, and that's about it. A great tool to help with this is the coder module, which knows about the API changes, as well as Drupal's coding standards.
I've added the GeSHi module for code syntax highlighting (apologies for the planet-spam caused by this), and I've moved from marksmarty to markdown + typogrify (which I had to port to Drupal 6). I'm not too happy with the geshi colour-scheme and indenting, but it does a good enough job. I should write a "command prompt" mode for it, but that can wait for now...
Akismet is currently totally broken for Drupal 6, even if it's labelled as being in beta. I got about half way through porting it before giving up and switching to mollom, which looks like a pretty good replacement (and it takes care of the sign-up form too).
Finally, the subject of input-filters. Drupal lets you define a "default filter", but that filter has to be available for everyone, even comments. So your default filter has to protect against XSS. I'd much prefer it if commenters used a simple, locked-down input-format, and I used a nice markdown format.
I'm not the only one to notice this, and it seems like it'll be fixed in Drupal 7. Until then, I'm using remember-filter which remembers that I use markdown, and all the commenters use the default, locked-down filter. (Again, ported.)