Go to phpmyadmin and look how big all your indexes together are.
Let us say your indexes are 100MB big, then set it to +50% = 150MB and look from time to time if you need to increase key buffer again.
You can add more indexes if you need. You have to look over each mysql_query($string) that is often loaded.
And if the query search on a not indexed column then add index to it.
Example1:
PHP Code:
SELECT * FROM users WHERE ip = $ip
if the column is not indexed then add index to it.
Example2:
PHP Code:
SELECT * FROM users WHERE class >= $class AND donor = yes
in these case you have to add an index over the columns "class" AND "donor"
Or if the where statment search over 3 or 4 columns you have to add an index over 3 or 4 columns.
You have to try which are the best indexes for you.