I have a Seagate 500 GB I leave on all the time. I have it set for performance. Things I did to eliminate unnecessary disk activity(and therefore the system trying to hold onto it) are, I have Windows indexing disabled... if you want to use it you may want to disable indexing from that drive.. what I used instead is Everything Search. It hooks into the NTFS journaling to get updated without indexing. Also I found
locate32 search updating was causing the drive to be indexed.. causing me to switch to Everything Search.
To make sure I flush buffers to disk I use
sync.exe that you can get from SysInternals. The Seagate has an activity LED. If that is still and I've flushed the buffers I don't worry about losing data. Basically the performance options just enables write caching. If you have battery backup and make sure to flush buffers or wait awhile before disconnecting you should be ok.
This doesn't take into account drives spinning up and down or any green energy saver stuff. I have the drive set to spin up and stay up all the time it's connected. If you have some power saver options then you'd have to experiment. But I've been running this way for over a year and I don't notice anything missing.