My concern is, I said something similar over a month ago.
Why be hesitant? Nobody ever died doing it (AFAIK).
Set your self a project to create a site, for example, your own site (which, as discussed, you will need). It does not matter if it does not work perfectly straight away if it’s your own off-line project for now, no one gets hurt. The only way you you will learn is to DO IT.
Going back the original question. Are you asking which layout, or which method to create the layout?
Q. Which layout? A. The layout you want.
Q. Which method? A. more loaded question. It will depend on the layout you want, how you want it to respond to smaller screens and the level of “old browser” backward compatibility you require.
Step 1, Consider your content.
2. Plan how to best layout and navigate that content.
3. Plan how that layout will adapt to a smaller screen.
At this stage you can choose the most suitable layout method: float, display-table, flexbox, ect…
4. Get Coding and make it.