For most new visitors, I'd say maintaining realistic expectations about "seeing it all" would be the hardest part. I totally think first timers are shocked at the actual size of Walt Disney World. It's easy to look at maps and pictures, but getting there and dealing with it is another story.
For me, I feel like I have a good handle on things. I know how we (by WE i mean ME, lol!) like to tour, I know when we prefer to eat, I know when lines start getting long and when to make FPs that fit with how we tour the parks...everything is pretty easy now, and the hard part for me is the lull in planning after FPs are made. Sometimes there's excitement when hours change (as happened to us for our upcoming trip), and ADRs need shifted or cancelled to keep us on track for what we want to do, but otherwise, the biggest challenge is the waiting!!
**editing to add...I based my answer on going in the summer. Our next trip after our upcoming July visit will be in December 2016. That will probably hold all sorts of challenges since I've never been anytime other than summer months!