You seem to be confusing two separate things: duplexing and booklet or n-up printing.
Duplex printing means that the printer will print on both sides of the paper. In other words, page 1 will go on one side, page 2 on the other, and so on. When you do that you have the option of telling the printer how the paper should be "flipped". For a normal A4 portrait page, you would normally flip along the long edge, so the pages will be able to be read like an a4 book. If the A4 document is in landscape format, then it is more difficult to decide which way it should be flipped, along the long or short edge, The answer depends on what you are going to do with the finished pages. Do you want to bind them along their long edge (the top) or the short edge (left edge)?
2-up printing lets you print 2 pages on each A4 sheet side. To put 2 (reduced) A4 pages on one A4 sheet, two portrait pages will be printed on one landscape sheet. For booklet printing the printer/driver also rearranges the pages so that they will be in the correct order when all the sheets are put together and folded in the middle. In this case you you may not want to bind them along any edge. For a booklet the thing to do is to staple them together along the centre fold. As the printer needs to flip the sheets to duplex, the edge to flip them over is the short edge. If they were flipped along the long edge, the back of the page would be upside down compared to the front.
If you are printing more than 2 pages per side, then it is important to consider how you are going to read the printed document.
In all cases, if in doubt about the correct setting, consider how you will be reading the document (portrait or landscape sheets) and how you will be turning the sheets while reading. In portrait cases you will most likely turn the sheets like a book (flipping along the long edge). For landscape sheets both are equally likely. In this case, flipping along the long edge produces a "notebook" style print, where you flip the pages up instead of to the left.
To repeat, think about how you'll be reading the document and decide from that which edge is the one to flip along.
I hope this clarifies it somewhat for you. I'll try to respond if you have additional questions.