Well, that depends on your system. clearly, you have to backup
/home/user/. /etc, /usr, /var and /opt are what I include. Some people say you should exclude copies of things you have in the cloud like your dropbox folder but I'd rather back it up and restore from a USB than wait for it to download over a wifi connection. You will have to reinstall any of your installed applications, but this is a good time to divest yourself of chaf of stuff you never really use.