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I see two main reasons to sue a specific ruleset:
1. There's a lot of pre-made 'stuff' like gear, skills, special rules, etc.
2. You like that ruleset and are comfortable.
Running Deathwatch in another system kills #1. #2 is still very valid: a lot of groups lean heavily to certain systems.
My main concern would be that moving to D&D (as a system I know better) you're trading one detailed system for another and you now have to improvise/house rule/fudge a lot of stuff to make it work. D&D doesn't have a Space Marine race or class, so you'd need to work with that. Realistically, they'd be a flat +2 to every stat minimum, a boatload of feats/skill bonuses, etc. Might be easier to call them 'human' and just say normal humans are -2 to everything... Which means that Elves can stand in for Eldar, etc.
Moving on to class... I guess 'Fighter' could be the basic Space Marine class. Mage for Librarians, Cleric for Chaplains. What for Tech Priests? Heavy Weapon specialists?
Mages and clerics aren't a great fit for Librarians and Chaplains. The 'theory' of magic is pretty different. a D&D Mage is lightly armed but can rewrite reality at mid-high levels. a Librarian grows in power much slower as they have to be on-guard for the corrupting Chaos influence and is generally less powerful, but gets the advantagges of being a Space Marine, power armor, access to good ranged and melee weapons, etc.
Much the same for Clerics/Chaplains. D&D Clerics can do a lot of outright healing powers, whereas a Chaplain is more a character that buffs allies, demoralizes, etc.
Speaking of gear, you'd need to develop and test stats for all the 40k 'stuff' like Power Armor, Boltguns, etc. And enemies, although you may be able to re-skin things here. Ranged weapons were never a major forte of D&D (one of the problems Iron Kingdoms d20 had)
On the other hand: if the group uses Death Watch as is the game is built with a lot of support for a group that's all warrior-types, possibly with some specialists. There's built-in support for Chapter-specific powers, and an interesting system that makes characters work a bit differently when part of a team vs. acting independently. There's special abilities and such for the various special Space Marine ranks. And lots of gear options: different Space Marine armors may have different features, weapon customization, etc.
The fine folks at FFG put a lot of effort into their games from what I've seen. I haven't played them, but I have the PDF of Rogue Trader and while they've made mistakes here and there, it looks like a good product and they've thought about removing not-fun things about the rules to focus on the fun parts.
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