Substance's ability to edit in real time is for the editor only, if you make a packaged game Substance's libraries doesn't pack with it, otherwise you would be giving every person a free version of Substance.
I don't know if UBER allows for this, I have never used it.

Have you used the Substance trail and some free models, to see if it works the way you want?

Actually with UE4 this is incorrect. You can edit directly in real time (game) using substance materials. You however, have to already have created the HLSL via Substance Designer. :P And any parameters you are modifying in real time need to be open for edit via Substance Designer. That said, no clue how it works for Unity

You however, have to already have created the HLSL via Substance Designer.

Didn't even think of this. If you made a HLSL shader with Substance and had a way to communicate with it then you should be able to use it in real time.

Unity has a Substance engine I believe to be comparable to UE4's. If the Substance has exposed parameters you can change them, and if the material is being used as a Substance(not as baked textures from the substance, as not all platforms are supporting it yet), you can change those parameters at run-time.

I'm no artist, but I can tell you, these softwares, if you learn at the least some basics, can help you make better graphics, especially combined with pre-made textures(like GameTextures.com textures). I don't think it will help with "hand-made" textures like some cartoon styles because those require actual art skill generally, while using pre-made textures and Substance Painter you can take a UV, mask off the UVs, and apply materials that can look good if done right. But this is more skill with software, not so much with actual art. It is like making textures/graphics relying primarily on Photoshop filters instead of actually drawing things with the brushes. It CAN work though in my opinion.

About Substance Designer, I think it is also a worthy investment. In theory it allows you to not be an artist and via the node system still create good textures. I haven't done much with it, but given time I've been able to make a couple things that I wanted to.

I honestly believe the LIVE Subscription is perfect for me. The $20 per month isn't much for me, a working adult with 3 children and a wife. But I had a bit of a head start, having learned basics of modelling with Blender3d, and knowing basics of UV mapping, etc... despite not having actual artist skill.

Thanks to everyone for all of the input. I'll have to review the full features for each software (Substance and UBER) to fully make a decision, and I'll also have to try out the free trial of Substance (I might wait until I actually am ready to add some Substances to my game, as anything made during the trial period is usable in commercial works. I know most of this will be time spent learning, but it might cut down on cost a bit).

Right now though, it seems like Substance is the strongest option.

I'll open another thread somewhere to discuss how I made out eventually.

Who knows, maybe some of you will also get a commission request from me in the not too distant future.