Before I play this game, I have a few questions....

1. Is everything fixed? I mean, are enemies placed or random?
2. When I find something in game - in a container/hacked from computer/etc, is that random or the same every time I start a new game?
3. Do enemies respawn?
4. What is the replayability factor?
5. Is there much grinding involved?

Any help is appreciated!

These answers are true for the main, official campaigns. Some UGC may contain far more randomness (in every sense of the word).
1. Yes, every enemy character is pre-determined.
2. As far as I remember, there's no random element in loot in the main campaigns.
3. No, unless you count a pair of encounters designed around constantly respawning hostiles.
4. I'd say that the Dead Man's Switch worth only a single playthrough, while the Dragonfall and Honk-Kong are closer to 2-3 times.
5. None at all: you do not gain anything from defeating enemies. It's better to think about SR:R as an adventure with tactical combat, methink.

P.S. It would be nice to remove duplicates of this question.

I am sorry, I didn't know I posted twice - I was having a problem with the site, but it seems to be working fine now.

I think Dilton meant you don't gain Experience Points for kills.

Well, I'd argue that this is still not exactly PC gaining anything by murdering as much as it is them gaining something by progressing through the scene which just so happens to be aligned with making some poor sods free from their prolonged existence (i.e. gaining stuff by killing isn't part of a core mechanic). You can't quite farm the hostiles for karma/money/equipment or maximise your net gain by first completing all quests in peaceful manner and then eradicating all life in the area once it became devoid of quests to complete a-la Divinity (I would concede to be an awful human being, but then, I'm also fond of finding Hidden Fun Stuff so that is a bit redundant).
And yes, I do agree that from a bit different PoV my statement is false in some circumstances - so sorry, I think.

And the Blitz backstory quest (in Dragonfall) will grant you either a weapon for combat in the Matrix, or in meatspace, but not both. There seems to be some not insignificant utility in replaying the games; I had to think hard before completing the central story of Dragonfall (how to treat the artificial sentience).

So, to answer the original question, Yes, there are a couple of thoughtful playthroughs.
I found grinding to be entirely self-imposed. What I mean is that there is a save-counter, incrementing every time a save point is taken (except the incremental progression save when one quits to the menu), and my natural perfectionist determination to minimize this number. Which makes the conversations (almost all of which are single-execute prospects, and exclude other conversational branches with each dialogue choice) necessarily repetitive (reload and talk to the character again). But, saving before the dialogue allows a simple restore to prime that conversation.

That one in particular is a great example as it significantly changes a number of things in the game from that point on - I'd even suggest it's definitely worth playing DF through at least twice just to experience each basic variation from that mission alone (though there are additional variations on those variations in a later mission as well). Not sure I would class saving/restoring a lot as "grinding" per se; "grinding" I would consider to be something akin to heading to an area with respawning enemies for the purposes of obtaining cash, loot and/or exp (karma). There are no respawnable enemies (not in the sense I mean here anyway), and enemies don't tend to drop loot or cash except in certain circumstances - so "grinding" is not even possible really.

I actually played it differently to what I would ultimately decide (for various reasons), so I have yet to replay and complete my preferred choice. (I'm about half-way in my next game, after completing the story once.)

Also a good game to replay with different character classes, too.

Not having played the PnP version, it took a little while for me to grok the modus ludendi (and the inexplicable "random" dice rolls that seem to accumulate fractional failure probabilities, rather than multiply them :).