Noise energy will always take the lowest impedance path back to the power source/regulator. If an adjacent device sharing a signal net has a lower ground inductance path, the only way to prevent noise on signal lines is to improve ground fill coverage between vias/pins on the first device. Keep anything that would increase the physical size of the current loop as small as possible.
If you signficantly interrupt the ground plane under a high-speed net, you will increase the inductance(loop area) of the return path. Periodically, a digital engineer asks me to isolate nets between domains. The mixed-signal engineer adds small jumpers across this isolation to be cut..and restored during testing. By the next rev, I have a single ground net again.
Get familiar with Cadence's excellent return-path continuity DRC. After all, you aren't using Mentor tools.
High-voltage potential situations are really the only valid application for an isolated return net. In aircraft equipment, devices that protect against lightning surges are intended to be robust and have their own return net to the air-frame ground (high-current ability and lowest impedance.)
In reply to oldmouldy: