This was my experience when trying to get fonts to look good in Ubuntu about a year ago. FontConfig, Gnome and of course some individual apps like browsers all have their own little settings for font rendering that interact in weird and not so wonderful ways.

I recently switched from Chrome to Firefox and realized that kerning is completely broken. I can only assume that it's because of some setting that I changed but I'd rather reinstall the whole machine than go on a wild goose chase...