Imo the most "challenging" areas to play through is the elite missions in factions, particularly The Deeps. Its certainly not the hardest in terms of strongest hitting enemies but I found it the most challenging. The reason I found it the most challenging is simply because of the co-ordination and co-operation required in your team to complete the mission. Your team has to work together to clear the mission, you can't just blindly go in and kill everything in sight. This level of co-operation makes the mission very fun everyone relies on each other and it becomes really enjoyable.
Once you've become experienced in the area and are going with a knowledgable team the area becomes much easier but if its your first time going there then it definately makes the area a challenge. Of course if its also you're first time going there it'll likely take around 4-5hrs to clear and thats after many wipes.
In terms of hardest area just in terms of chaos and mob strength I'd definately have to save DoA is hardest.
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