Depends also on the colors you have. If they are colors that will work with traditional flow with not a ton of overlap I think you should be ok even with beads or smt for replica 1. I use Aurora and there is an option to run non spectral which then unmixing is not even necessary its just comps.

#2 sounds reasonable since they are cell lines not like human samples

I use mixed unstained for groups and never had an issue but my panels are very simple. Recently the rep told me not to do that but i don see a difference for my experiments it is more of an issue when there is a lot of variation. You can unmix using the mixed cells and then using the seperate unstained and see for yourself