The main speed difference depends on if mysql can use an index for a query and how many rows that index forces it to scan.
The best thing you can do is take the actual query that is executed (after the code is compiled) and then add EXPLAIN to the front of it. That will tell you what indexes it could possibly use, what index it actually used, how many rows it had to scan, if it had to create a temporary table, etc. Lots of valuable information to optimize your queries.