There's a lot of minor changes, so I'll just list the most noticeable ones that will actually affect your item choices.

• General

  • Proc Chaining nerfed.
    • Only Ukuleles and a few other items can trigger other items.
    • Most items don't get increased range with stacks to prevent lategame instant map wiping.
  • Most on-kills can trigger on assists.
  • Some Uncommon/Legendary damage items are less effective when stacked.

• Notable Reworks

  • Crowbar

    • Procs on your first hit against an enemy instead of being based on HP remaining.
    • Damage bonus now affects procs.
    • Damage bonus lowered.

  • Delicate Watch

    • No longer breaks.
    • Lower bonus damage, now gives bonus damage when Out-of-Danger.

  • Power Elixir

    • Refreshes between stages.
    • Gives barrier instead of healing, triggers at 50% HP instead of 25% HP.

  • Berzerker's Pauldron

    • Applies a stacking buff on-kill, instead of being an all-or-nothing buff on multikill.

  • Lepton Daisy

    • On top of the Vanilla effect, now spawns a healing zone at the teleporter.

  • Old Guillotine

    • No longer executes, instead increases damage to enemies below 50% HP.

  • Old War Stealthkit

    • Reverted to pre-Anniversary behavior. (Chance to go invisible when taking damage, scaled to HP lost)

  • Squid Polyp

    • No longer procs on interactable use.
    • Now has a chance to proc when taking damage, scaled to HP lost.
    • Squids distract non-Champion enemies on-hit. (non-"Boss" enemies)

  • Hunter's Harpoon

    • Now works like in RoRR, where you can stack up to 25s of speed boost.

• Notable Buffs

  • Topaz Brooch, Berzerker's Pauldron (Rework), Infusion, Hunter's Harpoon, Soulbound Catalyst, Resonance Disc, Frost Relic, Brainstalks, and Wake of Vultures can trigger on assists.

  • Bison Steak

    • Increased bonus HP to 1 level worth of HP.

  • Personal Shield Generator

    • Shields gate against HP damage and don't count towards OSP.

  • Stickybomb

    • Higher damage and lower chance of falling off enemies.

  • Warbanner

    • Now increases armor and damage, and heals a bit.

  • Infusion

    • No longer has an HP cap (like in RoR1).
      • Every 100 HP increases the kill requirement for the next 100HP by +150 (100, 250, 400, etc.)

  • Leeching Seed

    • Heals for a small percentage of damage dealt. (before crit and other modifiers)

  • Red Whip

    • Gives +10% passive move speed on top of the Out-of-Combat move speed.

  • Shuriken

    • No longer steals band procs.

  • Aegis

    • On top of the Vanilla effect, now reduces Barrier decay rate as well.

  • Frost Relic

    • Bigger radius, faster radius increase per kill, longer decay time.
    • No longer messes with FOV.

  • Wake of Vultures

    • Gives bonus damage against Elites
    • No longer converts your HP to shields when killing Perfected enemies.
      • Installing EliteReworks will prevent it from messing with your HP when killing Overloading enemies as well, due to the Overloading rework from that mod.

  • Defense Nucleus

    • Constructs inherit the Elite type of the enemy that was killed.
    • Constructs distract non-Champion enemies on-hit. (non-"Boss" enemies)

• Notable Nerfs

  • AtG, Plasma Shrimp, Will o' the Wisp, Voidsent Flame, Tesla Coil, Frost Relic, Ceremonial Dagger, Molten Perforator, Charged Perforator no longer proc items.

  • Gasoline, Will o' the Wisp, Voidsent Flame, Razor Wire, Ukulele, Frost Relic no longer scale range with stacks.

  • Plasma Shrimp

    • Proc chance is now affected by proc coefficient.

  • Shatterspleen

    • Removed Bleed-On-Crit and Crit Chance.
      • Replaced with +10% Bleed Chance.

  • Shaped Glass

    • Scales linearly instead of exponentially.

  • Transcendence

    • Stacking beyond the first stack increases shield regen delay (due to Shieldgating changes making it a lot stronger).