Adding new layouts shouldn't add too much to the final size of your export. In most cases all three layouts can share the same images, videos, etc. If you are seeing your export size increase dramatically when adding a new layout let me know and I can take a look at your project.
This will scale your entire document proportionally. I recommend trying it out to see if it works with your design. Text, buttons, etc might get too small on an iPhone depending on your initial size.
Responsive Layouts and Flexible layout settings work great together.
Flexible layout settings can often allow you to use the same layout on similar devices. For example the iPhone 5, 6, 6+ can usually share the same layout (even iPhone landscape can often be the same).
But sometimes you need an entirely different layout when switching to a different device class like an iPad. It is difficult to define flexible layout settings that will work from 320 px wide to 1200 px wide. At some point things will get too squished or overlap. When you hit one of these points you can add an entirely new Layout and a new set of flexible layout settings.
I recommend using as few of layouts as you can, but the number is usually determined by the specific design of the page. A good target is 3 layouts (iPhone, iPad, and Desktop).