How is that combo different for client-side-auto-adjust testing? Testing one rendering engine for many sizes is STILL going to be easier than testing many sizes for say 200 rendering engines (browser brands x browser versions x OS settings, etc.)
Roughly 1/200th the work.
Also note one doesn't necessarily have to have infinite combinations: they could design for 3 sizes: small, media, and large; showing the closest fit. Sometimes you want to control what's shown anyhow for diff devices. For example, you may want to show fewer graphics or thumbnails for smaller devices to save room (phones & watches) than for tablets and screens.
User-adjustable client-side MDI windows or slide panels could also be an option for more complex applications. The MDI windows themselves could optionally be managed client-side. Treat each sub-window/panel as a mini application, in terms of how the rendering happens. (It does complicate the client a little bit.)
And one could also let scroll-bars automatically appear on the client for the vertical issue, somewhat like typical PDF displayers. PDF layouts are typically coordinate-based, but a vertical scroll-bar appears if the window doesn't have enough room to the show the entire thing.