Pretty much everything, from what I have seen thus far. It seems clear that the central organizing principle here is the circular plan. It's the kind of sexy form that Steve loved in consumer products, but plan abstraction is not necessarily a good place to start with architecture.
Several posters here have identified the most obvious issue, which is the vast scale of the building and the problems inherent with traveling from one side of the building to the other. Maybe Steve is having a conversation with God at this very moment and has persuaded Him to make rain fall less often over Cupertino, but failing intervention from the Almighty, employees in this building are going to be taking a lot of long hikes.
Second, the circular plan means that the building will be essentially devoid of the kinds of visual cues that we use to know where we are. Every angle of the building will look the same, at least externally. Internally I'd expect much the same problem to occur. This building is probably going to be very disorienting.
Third, the plan dictated the complete isolation of this building from the surrounding grid. It's a single, gigantic segregated land use requiring everyone who wants to do anything but work or eat at the company cafeteria to get into their car and drive somewhere else. A less dogmatic approach to architectural objectification would have accommodated a building more integrated into the place where it exists and have been more functional in that respect as well.
Those are just some of the more apparent functional issues with this building.
