This is not a good category for me. I'm usually pretty much OK with romances the creative teams put forward, assuming they do the legwork to set it up (and don't crap all over a different pairing I like in the process), so I don't spend a lot of time musing on hypothetical pairings. The one exception is not from comics (not originally, anyway), and that's Buffy and Spike, because Season 6 napalmed that pairing for me, then salted the Earth it stood on. I would rather see either character (but mostly Spike because I hardly give a damn about Buffy) with any other character. But that's more suitable to a hypothetical "least favorite canonical romance", and like I said, I don't really consider it a comic book thing.
To the extent I do consider possible pairings that haven't been romantically involved, it's usually characters already established as being friends. It seems logical enough to me that they were friends, then it became something more. The thing is, I can't shake two concerns. One, that there are so few legit platonic friendships in comics that it kind of stinks to turn one into yet another romantic pairing, and two, since I'm usually thinking of two female characters who are friends, that it's just some pervy thing on my part.
But you know what, I did think of one pairing that's never happened in continuity that intrigues me.
Power Girl and Dr. Mid-Nite.
For whatever reason, Dr. Pieter Cross is one of the costumed types Power Girl hangs out with the most in recent history from what I can tell, albeit almost exclusively in comics whose creative teams involve Amanda Conner, Jimmy Palmiotti, Justin Gray and Geoff Johns to varying degrees. But that's fine.
The two get along well, which is not something one can always say about Power Girl and other characters. The Doc is not threatened by the fact Kara is vastly more physically powerful than he is. Peej respects Mid-Nite's skills as a crimefighter and as a doctor. They seem to have an easy rapport. I feel like most characters' reactions to Power Girl's straightforward, confident personality fall into three categories: Mildly exasperated, admiring, irritated. Cross, probably from experience dealing with patients, just seems to accept it. He can enjoy talking to her, but if she starts to get defensive about something, he doesn't press. He recognizes that won't get anywhere with her.
Also, he's a moderately well-off guy with a strong community spirit, and Karen is a CEO who ran a company that tried to develop super-science that was helpful to the average person. I think the mutual interest in trying to improve the world outside punching things would provide some common ground, but there's enough differences they wouldn't overlap too much.
Also, Dr. Mid-Nite is a low-profile enough hero I don't think there's much risk of Power Girl becoming "Dr. Mid-Nite's Girlfriend", which is pretty important for the character, especially since she's largely avoided being a supporting character to a male hero up to this point. The nature of the threats they tend to face solo are different enough that, again, there wouldn't be too much overlap. They could each still have their own worlds, so to speak, and connect when and where it made sense. Plus, the adventures of Ollie the Owl and Peej's cat!
Power Girl and Mid-Nite react to this idea with predictable weariness in Power Girl #7. No, wait, they're reacting to the arrival of Vartox. Either way, the script is by Justin Gray and Jimmy Palmiotti, Amanda Conner is the artist, Paul Mounts the colorist, and John J. Hill the letterer. And the Doc had better consider his words carefully, or this thing is over before it begins in JSA Classified #1, by Geoff Johns (writer), Conner (penciler), Palmiotti (inker), Mounts (colorist), Rob Leigh (letterer).