I was thinking about this as well, but I am afraid the playing board(s) are probably too small to handle more than 4 players. Imagine, an extra player AND an extra monster group, that would fill those tiles up pretty fast. Since the scenarios mostly revolve around getting something or somewhere fast, a crowded board would be a huge advantage to the Overlord.
Maybe you could do a campaign where multiple players are Overlord and every Overlord player manages his or her own Monster group. Maybe this would also be able to solve the 5 player cap conundrum? One player could even control one of the luitenants.
Now what about the stack of Overlord cards? You could cut it in multiple stacks and give every Overlord player a stack. Every turn one of them would get an extra card. Or, to make it even more tactical, you could decide to give them one pool of cards and they have to decide amongst themselves how to use it best. Or… thinking even further outside the box, you could have one player manage the deck of Overlord cards and the other players manage the monsters.
Especially the last scenario could be really cool, because the player holding the deck would be the 'real' Overlord and the other players just his minions. The 'real' Overlord player could also be in charge of reinforcements and where to place them. In other words he would have the power to summon minions at the end of every turn.
This could make for some amazing team play on the side of evil, turning Descent into something of a Fantasy version of Memoir 44.
Now… how to solve the problem of getting such a large group together on a regular basis…