It sounds as if you are considering booking separate tickets to Paris or Amsterdamn and then on to Italy? If so, you should probably book to Italy RT, and the layover will be arranged by the ticket you purchase. The airlines will allow the correct layover time and they are then responsible to get you to your final destination if the first flight is delayed. You don't want separate tickets because if your first flight is delayed and you miss the second, you are resposible, not the airlines. You could also do a multi-city ticket, so stay a night or two somewhere going or coming if that is what you want.

You will go through immigration/passport control at your first Schengen point of entry, in this case, AMS or CDG. You will go through security there too. You will retrieve your checked bags and go through customs with them at VCE. If you decide to leave the connecting airport, you'll go through customs with whatever you have on you, but your checked bags will still go all the way to Italy.

On an international itinerary, you are allowed to have a layover (connection time) of up to 24 hours without having to pay extra for your ticket. So, you could certainly spend a few hours -- or even an overnight -- in Paris or Amsterdam. For example, if you wanted to spend an overnight in Paris, you could take a 9:35pm Air France/Delta flight from Detroit that gets in to Paris at 11:30am. Then, the following day, you could take a 10:15am Air France flight to Venice. If you did that, you could ask the check-in agent in Detroit to check your bags only to CDG, rather than all the way through to VCE. If you wanted to do that, it might not be possible to book that connection online, so you might have to call AF or Delta.

If you didn't want to go into Paris or Amsterdam, you can safely take whatever connection time your booking engine offers. In the unlikely event that you miss your connecting flight to VCE, you'll be automatically protected on the next available flight.

You will go through passport control at CDG or AMS on the way home as well (to exit Schengen). Your bags can be through checked to DTW.

Thanks for the helpful (and quick!) advice everyone! I think I'm starting to understand how the system works... I'll book my ticket through to to Venice on Delta's website, so it should be the same ticket even though I'm sure the second leg of the flight will be on one of their partner airlines. Some of the layover length options they give seem pretty short (just over an hour); I don't even like to cut it that close for flights within the US most of the time.
DonTopaz - the flight you mentioned is one of the ones I'm considering!

An hour is just enough for AMS and I suggest at least 90 minutes for CDG. Might as well book a late afternoon flight to VCE. Many trains for short rides either from AMS to Amsterdam Cantraal, or from CDG to central Paris.

Be back at the airport an hour before flight should be fine, since you'll have your BPs and only need to go through security.

As to your potential case of wine ... a couple of things to consider. First, your airline may want to charge you anything from $25 and up to transport it home (assuming you do not have status on the airline).

Second, you are permitted to import one liter of alcohol per person. Your case would probably be in excess of 2 liters so technically a 10% duty would be required. However, in many cases that would be such a low amount that Customs would simply waive payment (depending on what else you declare). Just be aware of this potential expense (and keep your receipt!).

You can fly nonstop to Venice out of the US-New York,Newark,Atlanta,etc. OR you could fly nonstop to Rome out of DTW and then a quick flight out of there to Venice for ease and convenience?

I would allow two hours at either airport. I much prefer AMS over CDG.

A couple of years ago, I scheduled a long layover at AMS on my way to Zurich and went into the city for the day. It's easy to store your carry on luggage (after you exit arrivals), go downstairs and there are lockers. It's a short train ride into the city. I think my flight arrived AMS about 7 or 8 am and departed for Zurich about 8 pm. I had been to Amsterdam before, but my traveling companion hadn't.

You'll find it difficult to pull up these layovers on Delta. You will need to select the multi-city function and enter each leg separately. DTW/AMS,AMS/VCE, etc. and search by schedule not price.

If you are returning from Rome, I would book the non-stop FCO/DTW.