Processing time is one. Reading from a file takes longer than reading from memory. Although if you don't do anything weird you will never know the difference.
Also, sometimes it happens that your variables get cleared. Happened to me several times, sometimes after mIRC crashed, sometimes after I closed it normally, but I have never been able to find out exactly why. It means starting over. That won't happen if you use a inifile.
These days I use both: I store everything in an inifile, and when I start mIRC I clean out my variables, and load the ones in the inifile. That also cleans up and variable-trash I might have left and don't need. Then everytime a variable changes I write it to the inifile.
