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Is this overkill?
I think the specs you posted are pretty reasonable given the number of email accounts.
SME will read 3GB of RAM per processor since they are quad core will it read 12 GB per processor? Should I go more RAM?
I'm pretty sure that the "hugemem" SMP kernel will support upwards of 16Gb of RAM. For that many users, I would definitely suggest a lot more memory if there are going to be a lot of users accessing their email simultaneously.
My old mail server has 2 single core processors, 2 GB of RAM and 2 mirrored 36GB Hard Drives. Should I go with mirrored or RAID 5? If Raid 5 should I make it Raid 5 + 1?
With an install this big, RAID 5 with spares is definitely a good idea -- RAID 5 gives you error checking, rather than just mindless mirroring. I would suggest at least 4 drives, maybe more. Each additional drive means less chance of a failed drive taking down the system. You can calculate the available space etc.
here.
If you are keen on keeping downtime to an absolute, you might consider hot-pluggable SCSI or SAS drives.