I've just discovered a nice bug (at least I believe it's a bug) in Miranda Portable Unicode v0.6.8 Built Mar 13 2007 11:25:24. The problem appeared when I decided to turn off the splash screen. I copyed the MirandaPortable.ini in the launcher directory and changed the appropriated setting.
When the problems came Any changes I made in the Options dialog were effective only for the current session of Miranda. After each restart they come to the values dating the day when I copyed the damn INI file. I'm sorry I don't have time to study the problem futher, but it seems like the profile become read-only when I use MirandaPortable.ini.
I hope this info will help you to improuve Miranda Portable. This said, I don't know whether it's a bug related to portable configuration or Miranda itself (if it's a bug at all).
I just notice the same problem and after some test i found that with the runlocally option on true the profil is in document and setting.
Try to put the runlocally to false on MirandaPortable.ini that work fine for me.