There are 2 versions of Prime Directive d20, one based on the D&D 3.5 PHB and the other based on D20 Modern. Are there any noteworthy differences between the two versions, or did they just make a second version of it for people who had d20 Modern but not D&D?
I asked on the Star Fleet Universe Discussion Boards, and received the following answers:
The two rules sets are somewhat different and while a good GM can make either one work with the other (after a fashion) d20v3.5 and d20M are effectively different game systems.
The two rule books (like all the Prime Driective rulebooks) share 60 or so percent of material. This being background, fluff, fiction, etc.
The rest of each book is system specific and there are enough differences between D20 and D20 Modern to require two separate books.
While both systems work for PD, I much prefer the D20M version. In D20M, your character classes are Strong, tough, Fast, Smart, etc. rather than Warrior, Mage, Priest, and Rogue.
The skills and feats avialable are more in line with a futuristic setting as well.
You can follow up if you have more questions at the Star Fleet Universe Discussion Boards.
As the other answer states, d20Modern and D20 are different systems entirely, albeit with some similarities.
If memory serves, d20Modern is built on the concept of the same six stats, but your 1st 3 levels are basically just a basic class specialized for one of the skills. You then have advanced classes that give special feats and abilities as you progress in them. The d20Future book added a lot of sci-fi tech and the idea of technology levels.
I won't cover all of the ins and outs of d20, as I'm assuming it's ubiquitous enough to not need a lot explanation. But it's definitely different from d20Modern.