As the author of the Leaderless/Targetless - Focus Based Hydra system and a user of the FTL system under Innerspace and a previous user of a targettarget based system I can tell you that I like the FTL the best.

When I was using Focus Based Hydra I ran into problems with my mages and being able to CC. Focus was taken obviously so I worked my CC around target based macros and it worked but wasn't as reliable as I'd have liked. All said and done it was frustrating to try and utilize.

The FTL system is VERY reliable, however it requires a significant amount of setup that I'd never have done without ISBoxers native support of it. The way I have it setup now is flawless, works in and out of vehicles, and has absolutely no drawbacks for me... the ONLY issue I ever have is when one of the clients (or all) get a chat box open, but tahts going to bugger ANY system since chat boxes eat keystrokes.