My 3 year old iMac is freezing and I get a message "startup disk almost full for running applications. delete files..." Where do I find the startup disk and what should I delete?

My 3 year old Mac is having trouble and freezes up from time to time lately. I get a message saying "startup disk almost full, delete files ..." something about having enough room for applications to function. I know my startup disk is the Macintosh HD, but what kind of files do I need to delete and how much space do I need to free up? In my "about this mac" area, it says I have 4.89gb free out of 319.21 So I am confused why I need to do this.