I have a couple of thoughts on this. First and foremost I would avoid spanning multiple drives into a single striped pool because if you have one drive fail then the entire pool is lost. So with that said I would only make multi drive pools with some type of redundancy built in (eg RAIDZx or RAID5/6)
Secondly as for How VMS's handle the drives, you should have no problem using separate drives (D:,E:,F:,G: etc..) In Milestone I would look in the "Configure Dynamic Paths..." area.
If you are going to utilize a RAID config be mindful of disk size and rebuild times when designing the individual pools. With current drive sizes being so large, the rebuild / re-silver is likely to reduce performance and possibly cause additional drive failure during the process.