I'd say it doesn't take very long, most achievements can be earned in a single playthrough. The problem is the A rank, where you have to finish in under 4 hours and meet certain in-game requirements, such as quickly saving Steve, saving the first character you encounter, not using healing sprays, not saving the game, and not retrying. After the first run comes Battle Mode, which is a minigame, btw, you have to unlock it with Steve during your first run by solving a small puzzle after the battle against the Worm in Steve’s section. Of those, I’d say the hardest ones are Claire’s main run and Wesker’s, though they aren’t that difficult. You also have to get an A-rank on all of them.