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.
• (AssistManager) 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

• 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.

• (RiskyTweaks) Shuriken

  • No longer steals band procs.

• Ignition Tank

  • Has a built-in ignite chance.

• 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.
  • (RiskyTweaks) 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).