Edit: not sure if this is the most efficient, but you get a generic t4iso every time you take the short path on the Act 4 Venom quest if you happen to have a buff controller (or someone with crazy dot) and can finish the fight quickly.
I used to ask this question and it sounds like we're at a similar progression point. Here's what I've found - to accumulate generic ISO, the story quest is best. Have you 100% explored Act IV or just completed it once? I know it's tedious but, if you've just completed once, start working on 100%ing. The rewards are good, you get a lot of ISO, and my understanding is that it will help prepare you for Act V. Even just 100%ing one map gives you a chunk of ISO. Long-term, it seems like duping 4*s is the best way to get ISO. So whatever will help you accumulate 4* shards. The squirrel quests are good for this.
Honestly, I'm gearing up for Act 5.2, so I don't know for sure. I think it's progression dependent. Exploring Act 4 is a great source of ISO, that's all I'm saying. It seems like you get chunks of basic ISO every time you run a map and definitely for each map and chapter that you 100%. But, if you can beat 5.2, it improves all of your rewards, so I'd say go do it as soon as you think your team is capable.
Comments
Edit: not sure if this is the most efficient, but you get a generic t4iso every time you take the short path on the Act 4 Venom quest if you happen to have a buff controller (or someone with crazy dot) and can finish the fight quickly.