I will try and answer your questions in order and with the Ety ER-4P (since it is a portable use) as the reference. The ER-6 results and answers hsould be almost the same.
1) I listen to the 3G iPod at no more than 1/2 volume and it is plenty loud. Any more than that and I get ringing and the slightly "pushy" highs of the Etys cause quick listening fatigue.
2) I have used the 3G while sitting, flying on a plane, walking, biking, on the train, and at the park with the dogs. I have had no issue with the vibrations caused by these activities. The 1.8" drive can be susceptible to the vibrations caused by running depending on how you hold it/where you clip it. The iPod drive will lock up if exposed to persistent vibration for 20-30 minutes and a soft-reset is needed to get it back -- no the end of the world. I am on my 4th iPod (5GB original, 20GB 2G, 30GB 3G, and a mini) without any issues whatsoever. I currently have both the 30GB and the mini, the other 2 were sold to friends after I upgraded.
3) 600 tracks is NOTHING with an iPod. I record my tracks at 256kbps AAC and have 3,000+ on the 30GB unit with about 8GB left to fill. I ripped 40 full-length CDs in a few hours one weekend -- it all depends on how fast your PC is. A cheap external hard drive is all you need for reliable back-ups if you are worried about the need to re-rip. I archive my tracks as FLACs (lossless CODEC) and store the FLACs with the AACs and MP3s on an external HDD.
4) You get used to the button layout in a day or so. The scroll wheel is only used for volume control when you are not looking at the iPod, and this is a "feel" setting anyway. The top four buttons will become 2nd nature after a little bit of use. I am to the point now that I do not even think about what function it is that I want -- my thumb moves before I can even process the command.
5) The scrollwheel and the buttons are touchsensitive and require a change in the electrostatic field on the pad/button to execute any changes. Inorganic items in a pocket like keys, change, etc. will NOT cause unwanted changes on the iPod. Vibration will also have no effect on the Pod. I have gotten in the habit of activating the Hold switch (top of the iPod) at all times so that I do not accidentally change anything when I have it on my lap when on planes. This also helps preserve battery life.