1) A smaller BKF file size will use disk space more efficiently (less wasted space in the last BKF file of a set) but a larger size will probably increase throughput (fewer pauses to close a file and open a new one).
I'd leave it at the default 4GB unless you can come up with a reaspn to change it. Let backupExec keep track of what physical disc a given BKF file is on
2) All of the data for a give resource (share, database, Exchange Store) in a multiresource job is considered a "backup set". If you have multiple resources in a given job (ands who doesn't 
) and and you have selected only one, then when each resource is finished, any remaining space in that BKF file is wasted, on the other hand if you have large BKF file sizes and small one off type job going to it, the over write date for the whole file is reset after each job, so you may have "unused" space sitting and not available for overwrite
I usually leave it at the default (100)
3) You can use different B2D folders, but since you rely on BackupExec to manage all your BKF files anyway, you could set up one folder per physical device. As long as you use different Media Sets for different job, some space can be released while other space stays protected
there have been several posts about BackupExec not spanning to different B2D devices if one fills up, so consider that when deciding on media set expiration dates
