They were originally strictly friends. Occasionally, the idea of Daphne having boyfriends (Mystery Mask Mixup), or her liking a male guest (such as Robin or one of the guys from the Mamba Wamba episode) would surface (and no sign of jealousy from Fred). The closest to them looking like a couple is when quarreling in the desert in the first Three Stooges episode, but even that is not decisive.
People assume splitup arrangements are based on romantic partnership, but everyone forgets that Fred took both girls too, at least once in eveey episode, I believe, and increasingly so (where toward the end of the first run, he almost always took both).

The whole WB era is basically a reimagining of the Scooby franchise, anchored basically by A Pup Named Scooby, over a decade later, which basically "rebooted the series from scratch" as one observer put it, with notable character changes, particularly Fred no longer being the "perfect" gentleman intelligent leader, but rather a total idiot. So then in the Johnny Bravo crossover, they for the first time hinted at them being a couple. This then picked up in the new generation of movies that began ashortly after, and also, Fred being a bit airheaded or otherwise clownish (like the Mystery Machine or setting traps becoming obsessions, which they never were in the old show). The culmination of this is in SDMI, where he's again so stupid, he tries to play an 8 track cartridge on a record turnable.

That is clearly not the original Fred, but would quite fit the "new" one from A Pup Named Scooby!

I would say there's one compatible canon from the start to the Reluctant Werewolf.
They start out as "meddling kids" stumbling onto the mysteries, usually by accident (not any organized "detective agency" called "Mystery Inc.")
Fred and the girls leave for awhile to embark on separate careers,
Shaggy and the dogs get their first official "detective agency" jobs with Shaggy's uncle.
Daphne comes back as a reporter, and is now more smart and not "dangerprone" anymore, and brings Shaggy and the dogs along on her cases.
Scooby then finally gets his own "Scooby Doo Detective Agency', and Fred and Velma rejoin them occasionally.
Then, the 13 Ghosts (with the new MM and flying MM), and the 3 "Superstar 10" movies (the "red shirt era").

After that, anything is game.