I think the biggest issue with bio5 is that it completely lacked the sense of suspense and buildup that every other game exhibited, from 1 to 4. There were no locations or bosses that just 'came out of nowhere' in the old games, everything was hinted at beforehand, often long beforehand. You always knew a new boss or monster was coming because of something you read in a file or clues in the environment. Notes describing plant42 and how to kill it, or the janitor's diary talking about the alligator in the sewer in 2, Richard and the snake bite, or 4's 'it.' It was scary because you expect something. Bio5 often dumps bosses on you with no prior buildup: congrats on fighting through this quarry, now we'll literally deliver a random bat/scorpion boss to you by truck. Surprise! After a lengthy turret sequence, El Gigante out of nowhere! Bet you didn't expect that! The only time I think 5 actually took the time to build up to a boss was the first uroboros fight.
Same with the environments, you could often see or read about future locations long before you actually visited them. Seeing the castle or island off in the distance in 4, the constant references to the factory or clock tower in 3, and so on. Not only that, but the way they wouldn't just force you to return to old locations later on, but they would always be altered or changed somewhat to play with your familiarity using newly accessible areas, different times of day, and different enemy types and layouts. 5 (and 6) had none of that. They're just constant forward progression along a linear path without giving you a chance to become familiar with any given location let alone use that familiarity against you.
Those were the hallmarks of the series for me, and everything after 4 forgot all about these things while everyone was arguing about controls and accessibility. To me this is the real spirit of biohazard that the series lost.