I've tried a couple of different ways and by far the easiest way for me is to just manually shrink each sprite in the layout editor (ie keep the sprite's full resolution for full HD and make the instance smaller by a factor of 1 / 2.4) and keep the game resolution 800x450. I have a 'dump' layout and size the first instance in that layout; each next created example, whether it's drag and drop or using the 'create object' event will then be created with the resize resolution that I want. Then, on upscale to full HD, the sprites all retain a quality appearance as the engine scales them to 1:1.
There is an alternative method, but I don't like it and I'll explain why (someone else might have found good ways to manage these problems and then it would be even easier). You could design the game for full HD and for the 800x450 export just set the canvas to that size at the start of the first layout, then set every layout scale to 0.42 at the start of each layout. Visually the effect should be the same, but window parallax problems can become apparent because of the scale effect and I've never found an easy way to keep the HUD aligned properly using this method. I mention it for completeness only....
I've attached a simple layout capx that toggles between 800x450 and full HD. I think the question about scaling everything at run time would work on start of layout but you would find it almost impossible to manage in the editor window, because nothing would align like it would at run time. All graphics were in the public domain as far as I could tell.