The biggest issue for me so far is that Firefox seems to have a multithreading bug using the GTK libraries. It'll just go unresponsive and hang, then GDB shows that all the threads are stuck in locks, several of them doing GTK operations.
I should file a bug report but I can't reproduce it very often. This never happened in Fedora 16.
I also had a terrible time with the Anaconda installer. For whatever reason, Anaconda would freeze up, also in GUI operations it seemed. Using strace on its threads would unfreeze it.
And when the GUI was working correctly it was less than helpful. I don't know who designed the new disk partitioning but they really could have done a better job. Such as just using gparted instead of their own incomplete buggy thing. I was trying to do a hybrid EFI/BIOS boot on a GPT disk label. I had to eventually give up and manually wipe the partitioning using fdisk before Anaconda would even attempt to work correctly.