If you are just using instances of the Html content feature, my advice would be to use just one of them on the page and do layout however you like inside that one instance. You can create content templates with different layouts to make it easy to re-use them in different places.
Building a page with a bunch of instances and using our panels for the layout while convenient also introduces more hits to the database, so it can be more efficient to just make your own layout inside the single instance where that instance uses the whole width of the page but internally has column layouts. This also gives you more flexibility because you can do whatever html tricks you like to make your layout.
For example the home page on this site looks like 3 columns but it is really just one instance of the Html content feature using internal column layout.
Hope that helps,