I've upgraded from CF9 to CF10 on a Windows IIS6 box.
CF seems to run, however:
1. the default document is not working (an url without "/index.cfm" is not working, adding "/index.cfm" solves the problem).
2. all url's seems to have become case sensitive, which breaks almost every single app I've build.
I already have re-applied the IIS connector and I've installed all the latest patches.
Not sure about the second issue.. but your first issue (not working unless document specified.).. did you go into IIS and make sure that index.cfm and index.cfml are part of the default documents?