I've been playing this a _long_ time, and here's some of the best advice you'll get, ego aside -
1. On PC, download the r2modman so you can load addons, and make sure you add PROPERSAVE - allowing you to save the game, and resume runs that get your internet cut off. Nothing is more painful than being balls deep into a multi-hour game and having it all gone due to an internet burp, or other interference.
If everyone dies, you have no save (which is just like unmodded); but if you 'quit' the game without everyone being dead, you can re-launch the game when you want next time, have the same people join, and a 'load' button will appear in your multiplayer lobby and you can simply hit it to resume where you left off. Example - you're in a two-person game, one of you loses internet... poof, your buddy is gone... the one that's 'hosting' simply hits the escape key, quit's game and it says it's saving.... then when you wanna refire it back up, you can with no game loss.
2. I play it with my best friend across the next, using voice comms. This is ideal because it's the most fun you can have in the game, and it allows you to sort loot easily for maximization. We know what goes to whom like clockwork.
We play Huntress & Engineer combo.
3. If you play it to death and reach the really high levels, it's best on PC and you're gonna need a 3060 or higher video card pumping the correct PCI channel level for max effect because the 'math' in the game after 3-4 hours of play gets insane and lag starts. This is super-true for the DLC they just came out with, which added all sorts of flying projectiles all requiring individual calculations by the hundreds.
4. The #1 complaint is getting "1-shot", but truth is you can't get one-shot the way the game's coded, but you can get 2-shot, which often is the same as being 1-shot, or get 1-shot with an ugly bleed... because it happens SO FAST you'll swear on your mother's life you were 1-shot.
There is a mod called 'stagger' that allows you to actually dissipate this a bit more if you're into that... or just try to suck at the game less.
5. Typically the game goes up to monster level 99 in hardness. That's the cap on vanilla/unmodded. We run a mod that makes it unlimited (set to 250,000 but that's impossible). We've had runs go to level 40,000 lasting 5+ hours straight before dying.
6. For you newbies, it's all about pace - you gotta make sure you get ALL of the loot each level to keep up with hardness, all while going fast enough to keep the game level timer from getting out of control and thus increasing hardness at an unbalanced level to the items you have collected. This means on early levels open 80-90% of loot, go hit teleporter to lock the level so enemies quit spawning, do that fast, then use the money you got from defending the teleporter to open the rest of the loot. That's efficiency. If you do portal too fast, however, and don't make enough money - you can't open all the boxes/loot.
Later on, money won't mean as much and the levels get real hard - so it's best to race to the teleporter, lock the level, and then open everything. But that's _later game_ stuff.
7. Learn what the 'newt' is, know most levels guarantee one, with some being in super-high places or remote stuff that you'd think was 'out of bounds, but isn't.
8. The 5th level (the one you see every 5 waves), if you hit the portal stairs (natural portal entry) it takes you to the 'boss'. Hit the newt instead, then hit the portal so you get a blue door, go to the 'store', and choose your next level instead of doing the boss level. The boss(s) in the game is stupid/bad/waste-of-time game enders. If you get the bigger bazaar mod, you get 2 random choices of the next level in the store... otherwise, you get no choice and it gives you a random level in the teir cycle.
9. Eutopia with the huntress: Get the TRANSCENDENCE blue Beatle item, which makes all your health into shields instead (awesome when playing with a friend so you both don't need to split the health items), pick up GESTURE OF THE DROWNED (blue snail looking item), which makes your 'Q' item auto-fire, and then get the 'doll' Q-item, called 'Forgive Me Please'. By having Topaz Brooches, you GESTURE auto-fires the DOLL, which sparks the BROOCHES and gives you crazy-awesome ever-growing shields. It's not a cheat at all, it's a perfect example of a great build using a designed combo. If you get the red item called "Soulbound Catalyst", it will make your doll pump crazy fast, causing you not to need more than one GESTURE and less Brooches. Always keep grabbing Beatles when you see them, just makes your SHIELDS (your new 'xp') go up and up.
ITEMS:
https://riskofrain2.fandom.com/wiki/Items#Lunar 
