Those kits are labelled quad channel because they are validated on the HEDT platforms, too. As for which config is easier to run, it depends on a variety of factors. The ASUS boards utilize T-Topology, which favors four-DIMM configurations. However, one has to account for the capabilities of the IMC, as there is significant variance between samples. That's why the safe rule of thumb is to opt for memory kits that are rated at least three ratios below the maximum frequency the motherboard is validated for. This generally allows one to use a two-DIMM or four-DIMM configuration without requiring lots of manual tuning. Obviously, if you opt for a lower speed kit, your chance of plug-and-play improves (unless the memory vendor is using lesser memory ICs and binning them too aggressively).
And yes, it isn't recommended to add more modules to a config, as XMP is configured and validated for a single kit only.