you dont have to take it off, but its so much easier to do it with the tire off. takes like 2 extra minutes to take the tire off, and that's if u take a break.

 

depending on what your doing and how big the wire is its better to run it through the stock grommet on the passenger side but like you say if you already ran your RCAs the other way it wouldnt work but its much easier than drilling through the firewall if you want a clean install. Ill load a pic of my underhood so you can see what i mean in my profile if youd like . Like i say though it just depends on how clean you want the install and if you dont have the length of wire put your inline fuse at the end of your power wire and go buy a few more fee tof the same type to make the run to your battery. my .02 cents.