Game design on Remnant 2 is great. I'm on my third play through and it doesn't feel like grinding because there are always secrets i missed, and the randomized events and story lines on each world mean each play through offers something different. I think a 4th play would start to feel grindy because I've probably just about played every scenario.
My recommendation is do not spoil the game for yourself. Play through the game twice before you start looking up anything you might have missed. There are absolutely bonkers secrets that are very hard to find, but trying things differently is one of the fun parts of the game. There are cool options for different scenarios that you can get many different rewards from, depending on what you do. Don't spoil the game by looking up builds and then how to get the items you need. Find things naturally and play with what you have.
I'd say skip the lowest difficulty. If you aren't great at shooters, start on the second difficulty. If you're good at headshotting and think you can reliably hit weak spots, play the third difficulty. The hardest setting is actually very hard and you need builds to make progress there. There are TONS of items, a whole bunch of classes to find/unlock and a lot of guns and mods, so you can come up with really cool builds.