@lizellelubbe you’re definitely right about the alignments. You can see those streaks around the edges of the particle in the worse map, for example. This kind of thing should really be expected most of the time, because the spatial extent of the box sizes is really significantly different (~2x or ~4x as much area), so the particles are not really commensurate with one another in terms of the background. Especially for 3DVA, the smaller box is definitely what I would choose (and for model building until the larger box refinements catch up in resolution).
You can see from the CTF images that the aliasing is probably not really affecting these refinements. The other benefit from the bigger box would be capturing signals delocalized by the CTF - a potential concern at higher defocus, but again seemingly not the limiting factor. (You still have a range of defocus values, and today’s CTF envelopes are less severe at high defocus). You might be able to improve the refinements in the larger boxes by forcing more iterations, or though continuing with local refinement (including of the whole particle).
Have you tried using conventional template picking on the low defocus images you do have? You might find a range of -0.5 to -1.5 or -2.5 to be sufficient. I’ve seen some very good structures come from very low contrast datasets.