I recently made the effort to upgrade multiple sites from WordPress 3.4.2 to WordPress 3.5. Unfortunately, along the way I encountered some difficulties.
I use Hostmonster as my web host. Hostmonster has integrated with the SimpleScripts service, which is similar to Fantastico. SimpleScripts usually does a great job of keeping things up to date, but it does not update plugins. The problem is WordPress 3.5 is incompatible with the version of the Jetpack plugin installed with version 3.4.2.
My solution is to go in and delete the old Jetpack plugin from the plugins directory, and then log into my dashboard and reinstall the Jetpack plugin.
The second major problem was that I had some sites using the W3Total Cache plugin, and I kept having problems getting the sites up again. I have seen the caching plugins on my WordPress sites cause these kinds of problems before. They seem to cause the performance of the site to become fickle. A little change in the settings can crash the site.
My solution is to install a new WordPress, and configure it to match the old one, which had been using the caching plugin. The next step is to link ye new site to the old database. Finally I move the new WordPress install into the old URL and I have generally removed unused plugins, and streamlined the site along the way.