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its possible, hard drives are curious beasts, so far (in recent years) i've only had western digital drives fail, i doubt though that two drives would fail exactly at the same time, unless they were abused physically, that way at least you could replace the bad ones, plus in a RAID setup the idea is to swap the drives out before they start to fail, so a RAID 1 with SMART drives, should give you lots of warning. so to keep costs lower, replace every other drive at 50% of the expected lifetime, say every 1.5/2 years or so.
SMART drives are supposed to be able to tell you when they are getting close to failing, you need to have the software and check it often to find out though. I did have a SMART drive that announced its own forthcoming demise, and it did indeed die later. you will probably need a hardware RAID 1 to hot swap drives though, i'm not aware of a software RAID that can hot swap.
not sure what you mean about reliability vs uptime, since one is dependant on the other ? do you mean you are ok with some partial data loss , rather than complete failure ?
Its the drive controllers + bios that control the 160GB, if the MB doesn't support it theres a number of solutions, some software absed, some hardware based, LBA48 support is required, you can always add a new controller card, some HD's even come with them once you go over 160GB, i believe the WD boxed do.
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