I love singleplayer games, a good, long campaign is the best -- but the fact is, multiplayer adds an unlimited amount of replayability, and solidifies the purchase as much as anything ever could. The thought of a multiplayer game with a cover system and modern setting with BEAUTIFUL graphics has me very excited.
I think I said this somewhere in the topic but, imagine customizing your own pirate/treasure hunter/spelunker. Then, either have weapon loadouts OR weapons to pick up all over the map -- you'd start with a 9mm and a grenade or two, and then assault rifles, shotguns, sniper rifles and explosives strewn about the map? I like the loadout idea better, but I could deal with 'old-school' gameplay as well.
Game modes, as an above poster said, most of them would focus on treasure. Sure, you'd have your classic deathmatch, team deathmatch, capture the flag...but then game modes where there's a relic to collect somewhere in the middle of the map and brought back to the spawn and held there for an extended period of time. Then, a game mode where one team has to control a relic they spawned with...almost like a 'VIP' type situation.
If I can think of this while brainstorming in 5 minutes, what could Naughty Dog do if they committed to coming through with a great competitive multiplayer? I don't see what's wrong with it. In theory, it's awesome. In theory. We'll see eventually, I guess.