Short answer: no, it's not always necessary.
Slightly longer answer: it's probably necessary for most scenarios.
Pro software like Adobe's Creative Suite and Apple's Final Cut Pro use lots of shortcuts which don't depend on modifier keys.
In general in these applications, modifier keys are still used for shortcuts to menu items (generally actions), but not for actions exposed as tools in the interface (which normally simply change the application's mode).
For example, switching to the marquee selection tool in Photoshop is done by pressing m, but actions like 'Select All' are Cmd-a.
They do use modifier keys for actions that are not the defaults for the function (using Option/Alt with the shortcut will do the next option in that tool's set, e.g. ellipse select tool).
The benefits of eliminating the need for modifier keys include being able to use the keyboard with one hand while using the other to control the mouse or graphics tablet. That's made especially easy because you tend to use the same keys a lot in those applications (e.g. pressing m in Final Cut Pro places a marker in the timeline, something you may do many times in a row, and which you need to be able to do without taking your eyes off the screen).
These apps, by virtue of their complexity, sometimes invent their own paradigms for many things, ignoring platform conventions. Even in these apps, however, it's important that no single key, when pressed, has a destructive impact on the document.
All that doesn't make it a reasonable choice for consumer apps, though. For most apps, it's going to be much more work to train users not to use a modifier key than to just add them to the shortcuts in the first place.
In a similar vein: don't expect Mac users to use Ctrl shortcuts!