My first post was a bit big and clunky, and didn't delve into a lot of details. I'll definitely download the free demos of the games tonight. But the idea wasn't really all that thought-out, just an initial concept with a few key points to try and make it unique compared to other challenges.
To help alleviate your fears of Players vs. The Big Four, I see most of their attacks are strong single target effects, and most of the AoE's doing only moderate damage. This allows melees to get in and fight if you have mobs taking the aggro, and as long as you play sensibly, you probably won't get wiped by AoE's.
I see all of the Big Four being red names, so no insta-kill or CC. To make the game a little more friendly to insta-kill and CC builds, a Reinforcement NPC that decides to attack and their mobs can be affected. Likewise, I plan the Big Four to come from a random list each time - maybe some of them are summoners, that conjure a small group of mobs right off the bat or periodically. For example, Dr. Rushmoore could call his elementals; just make it so that they do not have that rapid respawn like in the mansion quests. He can only summon the pack every X minutes or so. There could be other summoners that produce hostile, CC'd mobs (either when they first are spawned, or periodic, like Rushmoore). To keep it from getting too bad, these spawned mobs do not respond to the goal NPC/Item's mass aggro, and just trail around near their creator unless the players or friendly mobs engage them.
So, it's a little random as to if your build will cut it or not, which I think makes the game more dynamic and interesting. Get lucky spawns, and they fall right into your hands. Get some unlucky spawns, and you'll have to figure a way around it.