I use clear caulk for gaps where dark wood and light/painted wood meet. It won't emphasize the gap when it's dry. It won't conceal the gap either but it will seal it.

Have you contacted an exterminator?

The shoe should mostly conform to the floor, that's kinda the purpose of it. Maybe the floor is just too uneven but I'd try to press the shoe down where the low points are when nailing it, as you are able, to eliminate as much gap as possible.

I've never put caulk where baseboard meets the floor, shoe or not, but a little clear caulk wouldn't hurt anything as long as you don't mind the look.

" Probably won't keep bugs out either way, unfortunately."

Not at all, bugs shoould be kept out long before a shoe mould as at they point they are already in your house........................

I would not recommend caulking that gap. The caulking would shrink, attract dirt, and be hard to paint.

PVC quarter round is pretty flexible and would conform to the shape of the floor better than wood. That's what I'd recommend.

You could try caulking the gap behind the shoe molding first then install the shoe molding over that. The molding will hide the caulking!

Shoe molding was not properly installed - should have been nailed to the floor. Also, shoe molding should match the stain on the floor and not be painted. When painted, it will chip very quickly and look terrible.