Don't kill your players with high file sizes

The best way is to create a blank template for a tileset, maybe throwing some basics while keeping it under 256 colors, then optimize it for size (with adobe or something similar).
After that, you can create tileset addons, max your colors to 256 for each one and optimize it again, then just use addtiledef2 to addon to your set. Saves some major size by reducing color information per file. Be sure you don't overlap addons with that method though, it'll put you in a bind. Any questions, find me on Atrius.
Edit: I failed to mention this also keeps it open for more tiles, because you can replace certain parts by naming the addon with a different prefix.
