Quit iWeb, delete the preference file Home Folder/Library/Preferences/com.apple.iWeb.plist and drag the domain file from Home Folder/Library/Application Support/iWeb into the trash.
Make sure that you have run the iWeb updates including the iLife Support update.
Restart your Mac and run Disk Utility to repair permissions.
When you relaunch iWeb it should offer to create a new domain file for you and you can start building your site.
If you want to keep your old domain file, create a new folder in your Home Folder and drag it out of the trash and into this folder.
Once you have got iWeb working, you could try launching your old domain file by going to the folder you created and double clicking the domain file.
Before doing this, make sure you save a backup of your new domain file to another folder in your Home folder as iWeb will overwrite this.
The last site that you launch in iWeb is the one whose data exists in Home Folder/Library/Application Support/iWeb.
For more information on handling multiple domain files go to....
http://iwebfaq.org/site/iWebMultiplewebsites.html