Technically speaking not much is different in how a flash drive and an SSD work. They basically both read and write files without the use of an actual spinning disk.
HOWEVER where a flash drive is designed for external use, and therefore limited in speed by it's interface (USB generally) an SSD is designed for internal use and is, therefore, connected by SATA the same as a regular hard drive. This allows it to utilize it's speed much more efficiently and gets you the fast load times SSD's are known for.
As far as your other question, I'm not really sure how to answer that. How best to use things is entirely dependent on what you are using them for. Personally I don't use flash drives for much but file transfers (to other computers or for watching video on my TV,t hat sorta thing) however I have 2 external HDD's hooked up (1 USB 3.0 and 1 Firewire 800) for containing my backups and media files (movies, pictures, video I'm editing, etc).