This is the tricky bit. It all depends on what critters you choose to face them, and how you adapt their statblocks to jibe with the PCs' abilities. With PWL, all you have to do is subtract the critter's level from all hit bonuses, AC, saves and skills (if relevant). You'll also have to adjust their damage output, to compensate for the lack of striking runes and property runes.
Or, altenatively, you simply use less dangerous foes. It'll be a crapshoot as far as balancing is concerned, but the way you, as DM, run the adversaries, that's what will make the difference. Do you have the adversaries use every last action to mess with the PCs? Or do you have them occasionally spend actions to gloat, roar, hesitate or even move away to regroup or withdraw, depending on factors like self-preservation or dominance over other associates.
I have a feeling that your approach could lead to an exciting, challenging campaign, where the PCs never know if they can come out on top, or if they have to cut their losses and run. It'll require you players to adapt to the style of the campaign.
The real question will come when you try to decide how or if you will adapt spell power from spellcasters. If you simply ban spellcasting classes, you could have a gritty, tough-to-survive campaign. If you allow all spellcaster choices, spells like Magic Weapon will become go-to choices, since they'll have little access to runes that, in a standard PF2 campaign, are commonplace to the point of being expected.
Let us know how it turns out. And, if you play on a VTT, I would certainly be interested in trying to join your group, if only to see how it runs.