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Although, the completionist in me might never allow that.
Many elements in DD2 are still unbalanced and it will take many updates to fix them.
Here's a nice doc that showcases the tiers:
https://docs.google.com/document/d/1HiAz5dmWvb3B8EnklPzn6XRK2Lt4w_WtjYnzZYxvki4/edit#heading=h.w6fx2x4s2sw3
Trinkets
All 3 trinket tiers offer some of the best trinkets so you'd definitely want almost all trinket unlocks. If you are lucky you could technically skip on 10 trinket unlocks or so and have a less diluted pool.
Stagecoach Items
Only a total of 30 unlocks and again useful stuff in every tier so there isn't that much you could skip on.
Combat items
With healing salve being in the 1st tier you already get one of the best items here. Tier 3 isn't too impressive but tier 2 has some nice things in there with taunt monkey, dust, more healing and some "throwables" which are nice vs The General and The Librarian. That's probably the only category you would get a benefit by skipping the later unlocks.
Inn items
The pig and the 2 quirk removers are in the last tier so once again you kinda want to unlock everything.
Most of the tier 3 combat items are AoE versions of the previous tier, so yes, you do want to unlock them - particularly for on-hit builds, or setups emphasizing particular DoT types, given almost every fight is an AoE encounter or involves multi-target mechanics.
A max-target Fire Grenade is 36 damage compared to the 15 from Molotov, and even if the AoE only hits two targets instead of four, it's still doing more damage - and also applies more on-hit effects - so unless you're pumping ST grenades into a priority target, you almost always want the party-wide version for everything else.
Conversely, the chance to find either (or both) is better than limiting yourself to one version.
Dazzlers, Holy Water and War Horn are great, and even the Med Kit (when you have no Healing Balm) is preferable to having neither. Bone Saw and Javelin are considered 'Weapons', thus they can facilitate weapon-centric trinket effects or the Chiurgeon's set, and the Wilbur Flag is a solid single-target nuke setup.
Seriously, just unlock everything. The gain outweighs self-imposed limitations.
But do you need it vs a normal road fight? Sure, you can absolutely annihilate a road fight but you can do so without any combat item usage anyways. The main areas where combat items are really important are lair bosses (especially region 1), confessions and maybe the Exemplar. In none of these fights will you need aoe combat items.
I've done the fresh account Challenge multiple times by now and in different variations. By only unlocking healing salve, you get so many of them you will have around 4-8 for the final fight anyways. If it wasn't for Act 3 and the stealth dust, I wouldn't even unlock past tier 1 for combat items.
Apply that logic to healing salves, which you are less likely to use for standard fights compared to spare grenades, traps, crowd-control, token-poppers, and other utility while stockpiling for the finale.
It's stupendously easy to make sustainable teams that benefit more from aggressive items than they do buckets full of extra healing, and given the frequency of Oasis nodes and missions - especially with a max-upgraded altar that gives free water - it's not uncommon for you to collect stacks of water (or bandages/salves) for emergency heals and stress heals. One of my more recent runs involved discarding 10 x Water just to make space.
Librarian + Child are stupendously susceptible to DoTs thanks to multi-turns - thus you are typically better served by lobbing an ST or AOE grenade into them instead of sitting on a +12 Heal that you may not even use -- and the same goes for General + Leviathan, giving you the option to tap the root/hand + dotting the General/Leviathan with a combat item and make better use of your next turn. They're also useful against the vast majority of end bosses, and if you have an on-hit build, even better.
Healing items are always nice, but they're typically thrown into an item slot and forgotten about until a desperation scenario, which is preferably avoided - and they're commonly found regardless of your item unlock level. Meanwhile, liberal use of other combat items saves infinitely more health, and you're far more likely to use them throughout a run, even if you just want to 'get rid of them'.
Whenever I have excess healing items (Water, Salves, Med Kits, Bandages, Burn Salve, etc), I never equip them onto more than 1-2 heroes at any one time, often stockpiling the most useful ones for the finale, where they can be used during predictable burst mechanics.