@rockth - A good chunk of the development in Cafe/Coffee/eXpresso was done in the PortableApps.com Forums by several of our developers. I don't think you can directly handle mimetype handling without doing it via the registry. PortableFileAssociator was written by wraithdu over in the PortableApps.com forums and handles moving things in and out of the HKCU registry (not HKLM) to temporarily handle file and mime type associations. You decide when it goes in and out and I believe you can run it via script calls on both ends. A similar feature is about to land in the PortableApps.com Platform beta.
Our registry handling works really reliably. Even if the portable app itself crashes or the drive is pulled, our launchers still handle registry cleanup properly. Any existing keys are backed up within the registry itself (via simple and quick key move commands) so there's less chance of any data loss due to a pulled drive or file corruption. The only time you could have an issue is if the whole PC were to crash and we'll even have a way to handle that shortly as well.
If you ever notice any issues/bugs with the way our software handles registry entries, please let us know and we'll get it fixed. We hate bugs
Oh, it is worth noting that the current Firefox 4 and Thunderbird 3.1 releases allow you to specifically redirect mailto and http (respectively) to a program of your choosing and our launcher will portablize the selection. So, Firefox can be set to launch ThunderbirdPortable.exe for mailto handling and Thunderbird can be set to launch FirefoxPortable.exe. You may be able to do the same for ftp, etc in Firefox though I haven't tried it myself.