The load indices are all that change when a plugin is loaded earlier or later than it previously was, thus loading a new mod (regardless of load order) doesn't break one's save such that all the other previously loaded plugins are seen as new or anything. The save stores the data relative to to the plugin, so a plugin's load index changing will effectively not adversely affect the user. A YourNiftyItem reference, whether placed in the Creation Kit manually or created by a script, will remain in place even if plugins are added/removed/reordered.
It's possible however, if a plugin has multiple masters and the masters' load orders are inverted relative to the header's master list, for reference info to get broken. When all the DLCs are out, we should all be playing/creating mods with them loading in the same order to prevent this happening to plugins with multiple DLCs as masters. Then, if multiple mods are loaded which both have dependencies upon multiple DLCs, reference info will line up in both cases as their masterlists will be in line with the actual load order.
For instance, PluginY.esp could be in trouble when referencing forms from either DLC if its masterlist is out of order while PluginX.esp's references will work as intended:
[00] Skyrim.ESM
[01] Update.ESM
[02] Dawnguard.ESM
[03] Hearthfire.ESM
[04] Killer Bees.ESM
[05] PluginX.esp <--- Has Skyrim.ESM, Update.ESM, Dawnguard.ESM, Hearthfire.ESM, and Killer Bees.ESM as masters in that order
[06] PluginY.esp <--- Has Skyrim.ESM, KillerBees.ESM, Hearthfire.ESM, and Dawnguard.ESM as masters in that order
What makes the most sense, IMO, is to load them in chronological order of release, regardless of the order of acquisition.