Okay so I've just installed Ubuntu 9.10 (Karmic Koala) to my desktop. It's not going great.
The first attempt was an "in place upgrade". The reasoning behind this was simple. I had a lot of notes in Tomboy Notes that I didn't want to lose. Previous experience has taught me that Tomboy Notes doesn't deal with upgrades well. However Ubuntu One has a Tomboy Notes synchronisation feature. So the reasoning was simple. Do an inplace upgrade. Upload my notes. Do a clean install later if I need to.
After the in-place upgrade was done I noticed the PC was very unresponsive. minutes pass by while I wait for the top panel menus to respond. I don't know what the issue is. But the 32-bit version running on my laptop doesn't suffer from this problem. But hey! No problem. I thought I'd just do a clean install. Same problem!
Now admittedly I did preserve my home directory. So perhaps there's some sort of conflict with my old settings. So my next plan of action is to wipe the system clean and start completely fresh. If that doesn't work I'll install the 32-bit version. Perhaps the 64-bit copy is experiencing issues? Who knows.
It's not all bad though. I have an SLI setup. Previously this would mean I'd have to use the text based installer. But this time the standard live CD handled my dual graphics cards with no issues. The installer can even deal with RAID arrays like Nvidia Stripe. It will even offer to install Ubuntu to the RAID array.
Considering very little seems to have changed on the desktop, RAID and SLI support in the installer would suggest all the big changes (if there are any) in Ubuntu 9.10 have taken place under the hood.
Edit 08-11-2009: As I suspected some settings from my previous installation were causing issues. With a 100% fresh install everything seems to be working fine. My advice is, do a 100% completely fresh install. Remember to back up your /home directory first and anything else you don't want to lose.