You can use a directory link to put all the databases into what the user sees as a subdirectory in the Notes client. In the Notes data directory, create a file named <subdir>.dir where <subdir> is the name of your subdirectory. The first line in the file is a directory name which can include a drive letter (e.g., "e:\data2"). Lines after the first line are hierarchical names for people that can go through this directory link ("e.g., */MyCompany") so you can use directory links as a security tool.
You can also use a database link. To do this, move the database to your new directory. In the Notes directory where the database used to be, create a file with the same filename as the old database. In this file, put the path to the new location of the database (e.g., "e:\data\db.nsf"). When Notes accesses this file, it will automatically look for the database using the path you specify.
If you are using OS/2, you can install the Toronto Virtual File System (TVFS) from one of the many OS/2 ftp archives. This file system allows you to merge directories and files into a "virtual" directory that you can then use for the Notes data directory.
Note that all of these methods will slow down file access a little, but the slowdown should be negligible.