If you plan to change tunings between regular and drop-D tunings, forget using a Floyd Rose - its too much of a headache... Otherwise if you mostly play on a drop D, you can tune you guitar to just drop D and use it as usual.
For my band practices I do not lock the strings at the nut (but do not do any Steve Vai type acrobatics either). The tuning holds up fine on my guitar this way for mild, general purpose squealie dives. Also with a tuner, I can switch between regular and drop D tunings this way.
Either ways, set your guitar up for the most common tuning you use. This is because in a FR, tuning up or down makes the bridge rise or dip, causing changes in intonation.
-- My current rig
Guitar: '98 MIJ Ibanez RG520 QS w EMG 81/60
Amp: Laney LC15R Tube, Fernandes 20W SS
Pedals: MI Audio Tube Zone Overdrive, Boss OD3, CS3, MT2, HM2, DS2, CE5, DD7, TU3, Beta Aivin DD2 Delay, Dunlop Crybaby 95Q, Stranger Vol Pedal, BBE SupaCharger
Others: Yamaha RBX 374 Bass, Yamaha MM-6 Synth, M-Audio Fast Track, Shure SM-57, Heet Sound E-Bow Plus
Wanted(pm if selling): EB VPJr/Boss FV500L,Ibanez w Original/Lo-Pro Edge