First, security, be shure you have blokked external trafic in your firewall directly to the database. If you install some tool like phpmyadmin use something like fail2ban or some extra level of security like htaccess ip whitelist for example.
For performace wise it all depents on you application queries, database size, and the server resources (cpu,mem, io). You can start off with some default settings, for mysql there are a few standard examples for different servers (high memory vs low momory) inside the docementation dir (at least for mysql). There are tools wich can help you fine tune these settings, they analyse the log files and make some suggestions. Mysql tuner perl script for example is one I have used.