I've beaten the game twice with NPC mains now and I dont think it's as impossible as it gets hyped (though worth noting that I usually like playing Druid, who tends to be more of a support role anyways), it just means you need to lean on your girls/creatures/spirits more than usual. If you've already beaten the game before then you're probably ready to handle an NPC run.
Three bits of advice I will give though:
1. Don't pick someone who relies on dating for their mechanics (Shirotama, Phy)
2. Go for someone you either cant unlock normally or unlock very late into the game (if you're picking someone that you get really early then you're really just depriving yourself of an MC, unless you really like having two Pyrea's)
3. Your MC is always around for entering portals; if you pick someone Giant or Enormous you're going to enter very few portals in your run and you should plan around this (Story portals are always max size)
Personally, I'd recommend the following if you're still unsure but want to dip your toes in:
1. Aran Valys (possibly the easiest run you will ever have in Portals of Phereon); his energy blaster is a 0 mana 0 cooldown 1 AP massive AoE attack with huge range, and gets Sidestep. Even crazier, this skill is Inheritable, so you slowly segue from Aran carrying you through early portals to an entire team of magic users dealing 100+ damage twice each to half the enemy team. You'll still need a PiercingClaws girl to handle the Overseer though, if you go for the alternate end.
2. Overseer; you'll enter very few portals with her, and you need to kill the king when you can because he's going to recommend going to portals you literally cannot enter. At the same time she's probably the best tank you'll ever see, with the only caveats being that she needs lust resistance, you need to kill enemies with PiercingClaws first, and her armor goes down permanently when attacked.
3. CN_12 or Evyrya Valys; both have a Railgun spell that deals 3*MG damage, making them superb boss killers. CN_12 has fantastic growths which will allow her to outscale Evyra (especially because both railguns are on a 1 turn cooldown, so Evyra's sidestep is less impressive and she has very little to do with it down), while Evyra starts with 20 Magic, her railgun has double the range, costs no mana, and does not remove fight-long magic buffs. CN_12 also has Energizer (eggs start at 50% progress), which can help get your team rolling.
4. Guardian; getting access to Soul Drain from the start of the game gives you a great opportunity to max out genetics ASAP, breeding out very powerful units, gets around the MC weakness of getting no powerful genetic traits, and gives you access to Fission, which is inheritable and combos into multiple powerful spells.
5. Narah; decent growths, can mitigate Death, snowball Lust Resistance (at the cost of killing max morale), gives an alternate method to recruiting (for Hostile & Gacha runs), and has Water Path which can help a mermaid team make their way to enemies.
Note that playing as Vera does not give you access to Blood Magic, otherwise she'd also be a contender. Monsters/non-humanoid Spirits cannot be chosen, otherwise I'd also recommend Sky Worm and Horror.
