So, two questions:
1 - Is there a way to only allow a skill to be used if the player is NOT wearing any off hand item.
2 - Is it possible to create a group of exclusive skills? I mean you could have 3 exclusive skills(buffs) active at the same time, as long as they don’t belong to the same “group”?
1- as in, completely unarmed in the offhand? No.
Expanding on this, having a class/skill which works with nothing in your offhand is a tricky thing to do in GD, because your character will auto equip anything you pick up, so if you have a dual wield passive then any weapon goes into the offhand. A shield? A focus? Straight into your hand.
To work around this, I would suggest to create a new item, if you want it to block, make it a shield and just remove the mesh so it appears as if you only have 1 weapon equipped. Then this new item could have some kind of baseline skillmodifier that would apply to your skill. You can toy with this idea, but afaik this is the only way to achieve what you are asking.
2- unfortunately no, and there is no workaround this time… the closest I can think of is… If these exclusives are from different masteries, you can consider making a “hybrid” exclusive that requires each of those other masteries, something similar to what Ceno did for Zenith masteries.
Hmm. Complicated.
About the weapons, would it be hard/possible to create a new item category such as a 1h sword that “counts” as a two handed?
Another solution would be to change the 2h weapon running animation to be the same as the 1h weapon.
I wouldn’t have much problems with making the skills for 2h swords only, but that running animation, though 
You can’t create a new category of item or create a type that “counts” as another.
There are unused weapon types available though, if that helps at all. Spears and Staves, unused in GD, relics from the TQ engine. Though if you made any items with this weapon type, you’d have to update skills to use spears or staves. Doesn’t really solve your issue I think.
I see :/. Well, thanks for taking the time to answer.
Another workaround I was thinking about would be changing all 2h swords models(meshes) and inventory images to custom ones I will make myself.
Modelling the meshes and drawing the sprites is not the problem, making it compatible is.
Any tutorials on that?
I’ll start searching for something…