Honestly I think the nightclub multiplayer could be great (coming from a huge Metroid fan who owns every game in the series except for Pinball, and prioritizes item upgrades, isolation, and persistent world as the defining characteristics of the series).
I imagine a bit of an Assassin's Creed getting-lost-in-a-crowd kind of stealth. It'd be hard to pull off on Wii, though; you'd need hundreds of patrons, I think.
Alien music that could be at turns beautiful and agonizing whale noise blaring from the sound system in the central hub.
Amazing visuals in time to the music projected above the dance floor (some aliens' idea of dancing could be very creepy, insect-like, halting, Silent Hilly. Some could just stand in the middle of the dance floor staring at you).
Various alien/future sports on projected holo screens above the bar, could have a fun F-Zero cameo in the background.
Make it a dark scummy kind of setting, and yeah, I don't think having a booth full of Space Pirates would be too much of a stretch. Glaring at her as she passes, initiating a fight if she gets too close. This would be a rough kind of bar where it might turn some heads, but the music would continue and everyone would go about their business if Samus killed one of them.
I really like the idea of "isolated in a crowd" and I think you could do it well in setting like that, especially when the patrons are aliens, so you can't understand what they're saying anyways.
You could have different areas of the clubs populated by different species. The aural component would change dynamically as you moved around. Some aliens' speech could function as background music, like something out of Metroid II.
Some species could almost blend into the floor/wall like a barnacle, co-opting parts of the club for themselves, projecting a very territorial feeling. You can take that route, but it might trigger a fight.
Play it up, make it like each section of the bar is a different ecosystem, hell, it'd have to be given different species' life support requirements. Some areas could be super heated for silicon based life, others more jungley, others with low gravity, some with no gravity in free fall, etc.
Sonic baffles could contain the main DJ music to the central area, and it'd be a very abrupt change as you walk through the club. Some parts would be perfectly silent except for your footfalls, despite the flashing lights and huge crowd. There'd be this neat disconnect between what you're seeing and what you're hearing.
Private conversations in booths would likewise be shielded, but you could see them pointing at you and talking about you as you pass.
The escort mission idea isn't bad.
I like it. First off, make the "pop" star extremely creepy and alien, barely recognizably a life form (NOT humanoid at all, or bug like. Avoid cliches). The "music" it performs is like sheet metal grinding set to a Melotron orchestra.
Have 2 players. One is Samus, escorting the pop star to the safety of a shuttle waiting outside the club.
The other is an assassin with a sniper rifle, among other abilities. For argument's sake, make it Trace, the best of all around not very good characters from Metroid Prime: Hunters. He can cloak if he stands still, but uncloaks when he moves or fires. He also has a very close range melee attack that, if performed from behind, is a one hit kill on Samus.
The route to the waiting shuttle is different each round. The club is huge, cathedral-like. Trace can choose from dozens of vantage points.
The sonic baffles could come into play; they could mask the sound of a gunshot, or of Trace's footsteps behind Samus.
Meanwhile they're trying to evacuate the club in an orderly fashion, but of course people and aliens alike, panic.
I dunno, I just love the idea of asymmetrical multiplayer. Deathmatch is incredibly boring, and control point and capture the flag are getting there. Something that seems to be taking cues from Splinter Cell's asymmetrical multiplayer modes is a welcome change.