If you've installed the plug-in for Illustrator, you'll never need to use anything but Illustrator for your work.

Some things I do (disclaimer: I have only had my robo for some weeks, but it took me many hours to get this technique down, which is working quite well for me): I design my piece on whatever various layers I normally would use. I create two additional layers, one called "fold" and one called "cut" -- those layers are reserved for just those lines that I need the robo to cut or perforate on.

When your piece is ready to test, go to file, Cutting Master Robo 2 > Registration Marks. When you place your registration marks, make sure that the orientation selected is correct (ie, vertical or horizontal, depending on your piece). I read on one of these threads that it is best to give it a wider margin, but I have been having good luck with a margin of .70 inches.

Then print your piece with the registration marks (which will be placed on its own layer) (making your cut and fold lines invisible if you don't want them to be printed).

Place your printout on a backing sheet. The side with two registration marks will go into the craft robo first, the other mark will be on the near left, as you face your robo (if they are not that way, you probably have the orientation set incorrectly when you did the registration marks -- you just have to redo them).
Then make your cut and fold layers visible and any of your artwork invisible -- you only want to be able to see your cut and fold lines.

Go to File > Cut/Plot.

When you cut from Illustrator with the cutting master , there are four tabs -

First tab
I usually do not touch the first tab, but I have heard that on the first tab, you can select the size of your media, usually A4. Second section lets you scale the image to fit media or otherwise and the next set of controls you come to moving down the page has a Position setting for moving the image you're cutting. You can click the up and down arrows to move it or drag. This lets you see where the image will cut on the paper. You can change the orientation by clicking on the icon.

Second tab
Most of what you want is on the second tab. At the top, you'll select the radio button "By layer" -- under that, you should see your cut and fold layers.
Check the box that says "Enable driver option" and uncheck the "Single setting for all. Highlight your cut layer, select the correct paper weight and pick a solid Line type (1). Then highlight your fold layer, but this time, select Line type 4 to get a perforated cut that will allow you to fold easily (if someone knows of a better way to score, please jump in!).

Cross your fingers, then hit "Send," then sit back and watch your robo do some amazing things!