The first time I installed this game, it kept giving me a couple error messages when trying to run it. First it whined: "Please configure your system in the launcher before running FS2. The Launcher will now be started!" This happened even though I had just run the launcher separately. Then another window popped up saying: "Freespace2/Fred2 cannot be run from a drive root directory!" That would be it, game wouldn't run.
Having had problems with games in Vista in the past, I reinstalled the game to a different directory, C:GamesFreeSpace2. This solved the problem for me. Now I digress as to why it solved the problem...
Windows Vista has this annoying User Account Control (UAC) feature which is supposed to protect from viruses or somesuch. It does several annoying things, one of which is restricting access to the Program Files directory and everything there in. Newer programs work around this, but older ones like FreeSpace 2 can just stop working altogether. Disabling UAC is an option, but there are several no-nos about doing that. So anywho, just sticking games in a games folder seems to work.
Even if this doesn't fix your FS2 problem (my apologies) you should probably keep this in mind for the future. I'm gradually training myself to put all my games in my games directory... This is also nice because you can set up an exception to you virus shield for that directory, making the games load a wee bit faster.

If you don't want to install into a different directory, you can right click the game's folder in Program Files, click Properties, navigate to the Security tab, and give the "Users" group Modify permission. The simplest way I can put it is that Administrator accounts in Vista share some security settings with the Users group. So if the Users group doesn't have permission to write to a folder, and the game tries saving something, UAC will pop up.