Without significant AI improvements, the only two ways I see to make it harder is MANY more enemies and enemies do MUCH more damage.....but good players wouldn't have much issue with either. Already with a single other decent player, you can add Peaches and absolutely destroy any base, or encounter with ease. My son and I have done, bow/pistols w/throwables no extra health runs on both Hard and infamous, No death hardcore on Infamous, and generally just play on infamous with ease. Current AI and numbers can't stand up to a single extra player, so adding more who have to stay within 50yards of each other it seems, would break the game into even worse ease of play territory.
Would I like to see AI improved, and more enemies...yeah, but doubt the engine could handle it. I would like it for just normal play too, maybe as an extra difficulty setting or bonus add-on, as this game is too easy if you know how to play it. M60 suppressed, bow, .50 cal suppressed, 1911 suppressed and shovels means kill everything in game easily. So while I personally don't have enough friends playing the game to need it, it could be nice, BUT they would need a complete overhaul of difficulty and longer tethers between players.