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Smiter = extra single target damage against unstaggered enemies.
Mainstay = extra damage against staggered enemies.
If you frequently hit staggered things, Mainstay. If you frequently hit unstaggered things, Smiter.
Mainstay is good if you have guy with shield in team that runs bulwark. Otherwise is worse than smiter.
Smiter works in more cases.
Enhanced power depends on BP.
Never bulwark.
Smiter is good on siungle-target weapons. On any other you start loosing damage. Yet you also need to take into consideration how exactly your weapon operates and what attackchains yuo are using.
But generally, if you dont know, take mainstay.
smiter always as a general rule of thumb, because its always extra damage without any kind of extra thing you have to do. (only works in melee)
Mainstay is the next, but only if you stagger a lot (dual hammers, great hammer, shield weapons). Some of the weapons have an argument to be made to just use smiter (if availble) but it depends, great hammer for example could make great use out of smiter as the light attacks are very good against single enemies. (only works in melee)
Assassin is the third in line, you have no reason to pick this unless you are a class that crits a lot in MELEE or do a lot of headshots in MELEE (assassin doesnt work on ranged).
If neither is the case, the two above are more worth it.
If you are really good at headshots this is better than smiter, for critting a lot in melee you only put this above mainstay.
Enhanced power (works on ranged) if you just want a little more damage. Its either used for extra ranged damage or specific breakpoints (breakpoints only matter on legend/cata, especially cata).
And as the last thing, Bulwark, the reason why you use it is the same as Mainstay. But the problem here is that it adds less damage. The 10% extra melee damage taken on enemies can be very good for your teammates as they can kill them faster, but is wasted on ranged teammates.
In short.
If your weapon does a lot of stagger use Mainstay, otherwise Smiter.
If I'm not running enhanced power or assassin I usually run Smiter on almost all weapons because I deal more damage to the elites that way.
With that said, some weapons like elvish glaive and Victor's billhook do benefit more from mainstay that from smiter. Why? Well in case of Billhook, the special attack staggers the enemy so you do get more damage from mainstay. As for the glaive, if you are running glaive on Handmaiden, you usually do light-ligh-push combo, and your pushes do stagger hordes, so the mainstay does deal bonus damage. Also the glaive is already super powerful vs armor, but suffers a bit vs horde so boosting damage vs horde with mainstay will be more beneficial and will make up for the weapon's shortcoming, instead of taking smiter and marginally boosting your already high single target damage.
The situations when you can guarantee to get the advantage from smiter seems more limited. Ex, during monster fights, or killing stragglers/roamers, or singling out tougher enemies in a horde before anyone else touches them. But if you get some nice breakpoints I suppose it could be worth the trade off.
Two other problems with Mainstay; fodder enemies often die in a single swing making Mainstay useless, and most high cleave weapons don't actually do much damage beyond the first 1-3 targets, they effectively just stagger which means that Mainstay has no damage to boost to begin with. Both of those factors combined makes Mainstay inconsistent and niche even in its own role, basically only good on weapons that excel at horde clear so much that they don't even need the boost to begin with.
So basically, Smiter. Damage boosts are inherently more impactful against targets with more health, and Smiter specializes against Elites and Monsters who have more health. Meanwhile, Mainstay is inconsistent or often overkill for infantry. Honestly, if I was picking a high stagger weapon, I'd want Bulwark instead.
You kind of contradict yourself (assuming you're not fighting solo). That's exactly the situation that makes mainstay shine. Ex, you and your friend use high cleave weapons, your friend just charge-attacked a bunch with a 2H hammer, say killing the first 1 or 2. The rest are staggered. You follow up right after and get a nice fat 40% bonus, killing 2-3 and staggering the rest a second time, your friend attacks the remaining for 60% bonus damage. Throw in more friends in the mix and smiter becomes less and less effective because it gets more difficult to hit those untouched. Another player just needs to push once and the smiter advantage is briefly exchanged to mainstay advantage for all those enemies.
Why in this game would overkill be a bad thing? Yes, smiter is better for taking out the tougher targets faster. If that's your preferred role then I don't have anything against smiter. But most of the fighting is against hordes along side your friends. Looking at a clean and optimal solo fight, depending on the weapon, smiter is better. But in the mess that 4 players create in battle I still would prefer mainstay, unless going solely for a melee bosskiller build.
I see it sort of like this, Smiter has a faster start up time, but lower output in the long run. Mainstay takes a bit longer to wind up (faster with friends) but has higher throughput once it's up and running. Smiter wins the sprint, but mainstay wins the long distance.