General Tab:
I left this default for the most part. The "Forget Coordinates" button is helpful for when your colors aren't selecting correctly.
https://images.steamusercontent.com/ugc/10369729048590245523/A020056D5407CEB54184E1942C088E846EF1CCB1/?imw=256&&ima=fit&impolicy=Letterbox&imcolor=%23000000&letterbox=false
Painting Tab:
The 5th from the bottom. Disabling "Double-Click the mouse for improved painting accuracy" will make the art print much faster.
https://images.steamusercontent.com/ugc/18343845169336603095/9ED3C8CF78AC4CBC23E6E1ED3B6722445E9BCE40/?imw=256&&ima=fit&impolicy=Letterbox&imcolor=%23000000&letterbox=false
Experimental Tab:
This can also be left default for the most part. If you are having issues with Rustangelo not registering left clicks in general you can try to increase the "Engine cycle" and "Mouse-click up" delay.
Also, for "Painting brush type" I have been cycling between light and medium round, both of which are good for different art.
https://images.steamusercontent.com/ugc/15173820592848085663/1C18D79BCD3A1CC8691A195CEDF3E4A064945667/?imw=256&&ima=fit&impolicy=Letterbox&imcolor=%23000000&letterbox=false

You have 2 options for aligning your art for printing. The first option I will go into is the faster way:
For this method you will rotate the painting so it is as straight as possible and hold shift and right click to move the painting to the top right of the screen. I prefer this method only for art that will take less than 30 minutes. The reason for this is that most servers have an AFK kick system in place that doesn't take painting into account. I will get into this more in the next section.
https://images.steamusercontent.com/ugc/17645627699790487551/C4FB396B66F4BA4294DF75A35BFD8E2EDB47533E/?imw=256&&ima=fit&impolicy=Letterbox&imcolor=%23000000&letterbox=false
The other method, which I prefer, involves simply opening the sign and rotating it so it is as straight as possible, without moving it's position. You will know it worked because if you close the art and come back to the painting it wont change position. This is beneficial because you will be able to paint the sign when you are afk, while having the ability to pause it to leave the base and do things and return to resume the painting when you please.
https://images.steamusercontent.com/ugc/14751562172526308192/E5D18790ADEE1EAB4CA67B4C78BA5AEB3CD8864E/?imw=256&&ima=fit&impolicy=Letterbox&imcolor=%23000000&letterbox=false
You will also need to align your painting controls, which can be frustrating if done with haste. I am going to paste in the image directly from the Rustangelo website, which I think also pops up in the tutorial every time you use the program. I will add, you need your UI size in your Rust settings to be set to the default maximum value, or else the colors will not select properly.
https://images.steamusercontent.com/ugc/15453051061259279058/62BCAE6282BE72AD0F7050E53F97B186E184AEBD/?imw=256&&ima=fit&impolicy=Letterbox&imcolor=%23000000&letterbox=false

Finally, there is the issue with grid lines. Rustangelo has some pixels it is simply unable to print on. You will find if you use 1 pixel width your paintings are covered in grid lines. Before starting the painting process, set your brush size somewhere between 2 and 2.5 depending on the detail of your art to minimize the dead zones.

That's it, it should work! Less color/detail means it will be faster. Good luck!