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I have an older USB 2.0 4 bay Drobo in RAID with a 2010 Mac Pro regular HD & 16gb ram. When I am running lots of Waves plugins it will crash. Sometimes. Depends on how many tracks, plugins and how much automation/events I have going. I think the RAID is part of the problem but I know if I got a SSD to replace my internal HD my system would be faster.

Short answer speed of your internal OS HD matters. If you get a good external with USB 3.0 or thunderbolt it will be fast enough.
 
What is the best option for a 2-4 terabyte HD for this programs ?
Even today with larger (4TB+) there are times when you want to partition and just use half, keep everything with shorter seeks, use a couple drives. Then if you must go external I favor an SATA III PCIe controller and eSATA instead of USB3 card.
 
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