1) You can define in the Designer with Other any layout variant you want.
You can, for example, define a special layout for a 480/800 scale1.5 device if you want to take advantage of the extra space you have at the bottom of the screen. You can do this in a layout variant or by code.
I explain this in chapter 5 Screen sizes and resolutions in the Beginner's Guide. In the example it's done by code, but could be done in a layout variant.
What you cannot have in a same layout file, is having two layout variants with the same number of pixels but different densities (480*800 scale 1.5 and 480*800 scale 1). This is wrong, it is possible.
2) If you want to have one layout for portrait and one for landscape you can have two layout variants in the same layout file. All the views are in the different layout variants but at different places and could have different dimensions.
This is also valid for any other resolution.
There is an example in chapter 8.6 Layout variants in the Beginner's Guide with one layout file but two layout variants one for portrait and another one for landscape.
This could of course also be done by code.
You could also add all views by code without any layout file and set, in the code, all the positions and dimensions according to the different resolutions, densities and orientations.
In version 1.5 of B4A there was a layout 480 x 800 scale 1.5 (240) as a predefined layout, I just saw that this one is no more a predefined layout in version 1.6.
Best regards.
EDIT: This statement above:
What you cannot have in a same layout file, is having two layout variants with the same number of pixels but different densities (480*800 scale 1.5 and 480*800 scale 1).
is wrong, it is possible.