I'm completely new to graphic design; I'm looking to create impressive skins for forum software using CSS and Paint.NET. Should I steer clear of that, and pay for Photoshop instead? Is there any significant difference?
I cannot believe this question is actually asked this often. Assuming you're intending to use either of these pieces of software for website design (after all, we're on a web design forum) then there would be no doubt about it that Photoshop would suit your requirements better.
However, that does not mean to say Photoshop is the superior web designer's tool. There are many Adobe products such as Illustrator or InDesign that will suffice. Even more so Adobe Fireworks, considering it was crafted for that purpose. Though Fireworks may be limited, combining features from the Adobe Creative Suite would be a pretty powerful weapon.
If you're on a Mac (doubt it, wasn't aware you could get Paint.NET on one, but anyhow) then you should probably also take a look at Pixelmator. It's pretty - and performs better than Paint.NET, that's for sure!
If you are strictly limited to Windows though, I am yet to see software that can fulfill my needs as much as Adobe CS.