Limit the number of layers as much as possible. If higher quantities are anticipated, spend the extra time and money in engineering to insure it. Each additional size adds to the cost. Layout designers have considerable fexibility since hole sizes can be .007-.015 larger than component lead sizes. They limit stack drilling and drilling one board at a time greatly increases machine time.
Drills also break more often and plating becomes more difficult.
Holes .021 and smaller must be stack drilled 1 deep. Holes .022-.027 can be stack drilled 2 deep. Holes .028 and larger can be stack drilled 3 deep. Planned annular ring of .010 is a good design criteria. Allowances must be made for etching, lamination, drill position, front to back registration, and film instability.