What file format are you using for audio? For your tilesets?
If possible, use compressed formats for these. Instead of using High-quality WAV or MP3 files, use WMA or OGG files. Instead of BMP files, use GIF or JPG files (as long as they work). The downside to using JPG files is that they don't tile well.
Don't have excess black space in your tilesets. If it's too tall, shorten it. If it's too wide, make it skinnier (using the Tile slicer from the tools menu). This is a huge space-waster.
If you have a lot of very similar large tiles, with only a small difference, you can simply create the large tile once, and create a smaller tileset and another layer over top of the layer with larges tiles to show the diferences. This will also allow you to create more varying tiles.