Does anybody need the 6th epidemic card in Pandemic?
We play with six epidemics most of the time and win about half our games, which is a good ratio for us.  My husband and I play a lot of two-player games, but we also play with three and four players and use six epidemics unless we have beginners.

We use a house rule of dealing two roles per player and letting the players choose.  Discussion is permitted.

The key to playing with six epidemics, in my experience, is to be ruthless in not wasting actions.  Yes, that isolated city with three cubes will have an outbreak soon; absorb it if you've got spare capacity so you can focus on getting the cards together for a cure or attacking bigger problems.  It can be tempting to say "while I'm in the neighborhood anyway why don't I...?", but you should always look at whether there are more pressing demands first.