If you think of a connection is defined by the tuple (source_ip, source_port, destination_ip, destination_port) then you might run into problems if destination_ip was a single value, just because whatever hashing you are using/table lookups for connection management, DoS protection etc. etc. might have problems with the sheer size. We are doing a huge amount of traffic and I can imagine having to engineer around some things related to that.

But the real issues are the ones that outline above.