As far as killing the guys off this is the first update that's supposed to have consequences to it. In the last update you could kill them but it didn't impact anything so I have no idea when would be the best time but for me personally I would try to do all the "side quests" first before getting locked in to any storyline.About drugging mom, in my run, I did not do it but also I don't remember having a second chance to do it.
Now, regarding the path, definitelly the routes locks out if not done properly, should I follow both mom's and bigsis routes as soon as they appear and then go with lilsis?
darn, I'll have to go back to the first weekend then.
When should I kill Bruce and Davide? Is it suggested to kill them?
Thanks a lot for following and helping me with my problem, really.
As far as the relationships, I'm dont think you have to do them together, you could just focus on Cassandra till her story catches up to Nicole's and you should be fine. Though for me I played more of the saz mod version so there could be inconsistencies.