I got the itch and started replaying the RE4 Remake after finishing Requiem, and I have to say, as someone who doesn't get too involved in shipping stuff, I really enjoy the idea of Leon and Ashley ending up together before RE9.
To me, they have the best chemistry and bond in the series, and it's made playing the game again really enjoyable. Lots of little moments of them building trust and fun back-and-forth comments, a few instances of flirting from both sides. Capcom obviously restrained from overtly leaning into it, but I think there is a very deliberate romantic undertone to how RE4 portrays their relationship. It's all over the game.
Unlike what seems to be the consensus, I don't interpret the ending as Leon turning Ashley down romantically out of disinterest - he keeps things professional with her, yes, and given the circumstances of his life at the time it's not something he would/could actively go for, but there are moments where there is that chemistry and attraction from him.
Instead, I feel like it's more of a bittersweet inevitability that their little adventure(nightmare) has come to an end, and they'll have to part ways. Towards the end, Ashley asks for reassurance from Leon that they're a team, and shows her eagerness in maybe following his line of work. But in that last scene you can tell Ashley is a bit somber and she asks if he wants to be on her detail somewhat rhetorically, already knowing the answer.
Ashley is the President's daughter, and Leon is a clandestine agent who is effectively forced to work for the government and do whatever they want. There is no future for any sort of friendship or relationship immediately after RE4, and they both know it. But it's not something set in stone.
I feel like, despite the obvious horror/trauma of the situation, they both would have a sense of "what-if" and look back with a bit of wistful fondness at their time together, sometimes wondering what the other is up to. It's very narratively satisfying to think of them reconnecting like 15-20 years after Spain when they would be more free to pursue something.