Generally you can completely remove all fonts without any problems.
Exception:
If there is a special character in an ebook (e.g. from a foreign language or a mathematical formula sign: ı, ƾ, ؾؾ, ∑ or similar), you can at least reduce the size of the fonts by using a (built in) Calibre plugin. I don't know the english name of the plugin. In German language it is called "Bücher perfektionieren", translated anything like "make your book perfect". This plugin deletes all unused letters of the font and it additionally reduces the size of the images.
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