For some reason, this has happened to me also after playing the game using Helifax's fix. It can be quite puzzling.
For some reason, something doesn't change skrimpref.ini back. For example, my horizontal rez is set to 4064 in the ini. However, sometimes the game will change and leave it at (1354--the rez of a single monitor). When trying to run the game again, it won't load at all.
Simply double-checking skyrimpref.ini to make sure it still has my screen rez correct, (4064x1020) always fixes it for me.
I know, this one can be really frustrating/scary until you figure out what's going on. just don't do anything drastic. :)
HTH
somehow i managed to broke the game... now when i tried to run the game without any fix.. it pops up
"Failed to initialize renderer. Your display doesn't support the selected resolution. Please set a different resolution in Skyrim's Launcher under 'Display Setting'.
Funny thing is, I already set it to 1680 x 1050... something screwed up my pref file or something, i dont know..... SIGH