I guess you can say all Etrian Odyssey games had a skill or two that could be abuse-able or in other cases, skill sets that were broken. I would say the move for Etrian Odyssey 5 is...
Necromancer's Zombie Powder to Equal Exchange or Merciless Shield (rough translation).
Oh, and spoilers on boss stats and such. No story spoilers.
To begin, this is the reason this is so powerful.
Zombie Powder - Instant Death; creates a Zombie/Ghost that has the same HP (max 9999) as the remaining HP of the monster that was Instant Death-ed
Equal Exchange - Destroy 1 of your Ghosts and do set damage equal to a percentage of that Ghost's HP
Merciless Shield - The selected Ghost takes damage for the entire party
By using Zombie Powder on FOE, you can create Ghosts with huge amounts of HP. You might think, well, FOE have good resistance to this type of stuff, but there are FOE around that can be quite easily affected by it. For instance, the Worm FOE in Stratum 4 is actually WEAK against Instant Death.
Equal Exchange does set damage depending on the Ghost you sacrifice. At Level 1, Equal Exchange does 50%, but Level 10 does 100%. What that means, is that you can do 9999 damage by simply sacrificing one of your Ghosts. And you can have 3 Ghosts at a time. Which means you can possibly do 9999 x 3 damage on the first turn.
Merciless Shield is just as overwhelming with a FOE-Zombie Ghost. Imagine being able to negate the 1st 9999 damage your party receives. Heck, if you have 3 Ghosts, that means 30000 damage can be negated before you have to do anything to avoid damage.
To put in actual numbers, the easiest and earliest pray for Zombie Powder is the Giraffe FOE in Stratum 2. He has around 4500 HP, meaning you can create 3 4500HP Ghosts right here. The Stratum 2 boss has less than 7000HP and gives the material for the strongest sword in the game if you defeat him in 1 turn. In other words, you can easily achieve this through Equal Exchange as early as during Stratum 3 (with 2 Necromancers using Equal Exchange, or 1 Necromancer and the rest of the party attacks).
Stratum 3 boss has around 13500 HP. In other words, if you shoot 4500 x 3 at him, he can die in 1 turn (with 3 Necromancers).
Once you get to Stratum 4, you meet the Worm FOE that is weak to Instant Death. He has enough HP to create a 9999HP Ghost. The Boss has around 21500HP. Store up 3 Ghosts and go fight him. You can kill him in 3 turns, or 2 turns if you use two Necromancers. Heck, 1 turn with 3 Necromancers.
Stratum 5's boss has 35000HP, so you can't take him out with just this method, but you can get to around 5000HP.
And don't forget, you still have other party members that can do whatever while your Necromancer(s) do this.
And the thing is that the only thing you have to do is prepare beforehand. Zombiefy the FOE and drag your party all the way to your target FOE or boss.
With this method, you can take out almost anything with just these Ghosts. Only Stratum 5, 6 boss and 1 Stratum 6 FOE has enough HP to survive 9999 x 3.
The more Necromancers, the more efficient. If you have 3, you can Equal Exchange 2 Ghosts while you Merciless Shield the remaining. That means 9999 x 2 set damage + negation of 9999 damage to your party on the 1st turn alone.
Anyways, you kinda get the idea. Be it shield or be it ammo, having 9999 Ghosts around is incredibly powerful. That said, abusing it may make the game a bit boring for obvious reasons.
Here are the basic steps... and it's quite easy.
First, you need to unlock the Second Name, which means this becomes accessible after Stratum 2. Zombie Powder is in the Spirit Destroying (rough translation) branch. Of course, ideally, you want Zombie Powder and Equal Exchange at Level 10.
To at least get Level 1 of each, it takes 7 SP to reach Equal Exchange and 15 SP to reach Zombie Powder. To get Level 1 of both, that is a total of 24 points, which is possible by Level 22.
Next, you find a pray that can be killed by Zombie Powder.
And voila, you get an overpowered Ghost. BTW, the Giraffe FOE above only gives around 4500 HP. The image below is not a continuation of what happened then, but I wanted to show HP9999.