About the 2 best friends. Do I need to note down every BF a household member has and should this be taken into consideraton after this person dies?
Yes, you need to note down every BF a household member has. Example: if heir #1 John is best friends with Adam, then Adam cannot be claim as best friend for any of your heir. Even after John dies, Adam still can't be best friend with anybody in your household. Unless you don't claim Adam for the requirement, then Adam is free to be best friend with anybody in the house.
I've currently had only one person died in my household and don't remember exact details, don't think she made BFs with anyone else than her relatives.
I find the safest way is have your active heir find 2 sims that has never met anybody in your household before, and make them best friends for the requirement. Keep those 2 away from your family.
Female founder accidentally became BF with Heir 1's boss who I wanted to use for requirement, but I've soon discovered that he has BF statue with someone else, so I guess he should be okay.
If heir #1 has 2 other unique best friend, then you are good. The main thing here is must be unique, so heir 1 boss is best friend with heir 1 and female founder, thus making him not unique. The boss will be illegible for the requirement.
However, am I allowed to use SN app or mean interactions to get rid of a few BFs of other household members and make one of them unique BF with my future heirs?
Unfortunately no, not allowed. Once you are best friends with someone, you have to count them. If you have SN app, its not hard for your active heir to find 2 other unique best friends.
I've had his potential spouse moved in (asked by the heir) and kept making her young enough for pregnancy before requirements are done. I've also tried extending the lives of a few original townies using young again potion drinks. Are these ok as well?
Yes. Main thing is you don't lengthen the life of your current active heir before his/her requirement is done.
I am sorry to hear Snufflesxx's glitch and is considering to use elixirs instead for potions, so can I leave out alchemy (as well as charisma, it's useful) for future unique skill challenge requirements?
Yes, you can leave out any skills you choose. So you can have alchemy and charisma as free for all skill, all your heirs can level it. You just need to make sure you have enough unique skill challenge for all your heirs (16). 3 skill challenge each, that's 48 "unique" skill challenge.
Do all 4 large tombstones, career rewards and 4x4 collections need to be contributed by founders and heirs?
Yes, all needs to be contributed by founders and heirs. Only exception is the income part for buying properties and buildings, household members can help out with making money.