[dba-VB] Which .Net Framework Should I Use?

I am just starting to learn VB.Net using VS 2008.  All things being equal,
I'd like to always select the latest version of the .Net framework
(currently 3.5 SP1).  My goal is to convert my Access system to VB.Net for
any new and potentially for existing customers.

Is there any reason not to use the latest version?  Like for some reason
customers don't want it?

Any thoughts on this?

Thanks!
Dan