Sorry to bring up this old thread, but Google brought me here

Got the same problem, Calibre hangs at starting up "initializing user interface".
Solution:
1. Uninstall Calibre
2. Delete AppData\roaming\calibre (AppData is a hidden directory under your user home directory, normally C:\Users\[your_user_name].
3. Re-install Calibre
It should work now!
How did I find this out? The portable version always works on my PC, and I figured there was some old stuff which was not compatible with the newer version of Calibre. And I found that.
UPDATE: only delete gui.json under AppData\roaming\calibre is good enough for me.