I run Ubuntu on 4 computers in my house, and on my laptop at work. I did a fresh install on my main workstation of Ubuntu Studio 9.10 x64.
I've had several serious issues, and I'm considering downgrading to 9.04. Occasionally nautilus will switch from clearlooks to what looks like a default theme, with larger fonts. It's distracting to say the least. When I reboot, my dual monitor setup reverts to single monitor mode.
While those are pretty minor problems, I'm concerned that there might be more issues under the hood.