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If I had to pick the gun I think the the most powerful without considering ammo consumption it would be Matilda the thing is basically a machine gun but it absolutely eats up ammo and ammo drop isn't always abundant enough to feed it and I've had times in my HG only run where I run out of ammo and barrels to break using it.
After that it would be Blacktail. I know Red 9 does more damage but its got such a horrible bloom in comparison. Red 9 was way stronger in RE4 original since it also had a laser sight with the downside being it had a high recoil but in the remake it has a high bloom even with stock. Original red9 was easily top in my opinion.
Worst gun for me is punisher just because of its over all low power and how niche penetration is. It's useful to break shield units but not worth upgrading just for that imo. I would rank it higher if the penetration can actually be used to hit regenerator but as far as I can tell neither LE 5 nor punisher seems to be able to pop their weakspots despite being treated as weapons with penetration.
So tldr for me
1. SG/Sentinel (I treat them as the same weapon since one of them is DLC and unobtainable through in games means and they're functionally the same weapon)
2. Matilda (only down side is how much ammo it eats up)
3. Black Tail
4. Red 9
5. Punisher
https://steamcommunity.com/sharedfiles/filedetails/?id=2958167358
https://steamcommunity.com/sharedfiles/filedetails/?id=2966260398
I have not done ng pro run with loadout included Sentinel Nine/Punisher/Blacktail (I'm doing Blacktail in current run), so I will not be making tier for pistol.
1. Its damage is actually only 2nd to the Bolt action.
2. It's very cheap to upgrade due to mag reload, and no firing-rate upgrade.
3. If you lightly tap, you can do 2-round burst with, which is the most efficient and damage-burst of all weapons (even more than magnum).
4. Last but not least, it spawns rifle ammo due to the huge capacity.
I think it's only flaw is that you get it half-way in.
Nowadays hudless is the rage but I want my cool looking hud.
Which is why I opt to at least once use each weapon on ng pro.