Set up two rows of chairs and start playing "vacation." Your goal will be to slowly increase their tolerance and expectations for staying in the car. Include some of the activities they will be able to do in the car. Make sure when you get out, you use the same rules you will have on your actual trip, i.e. you can run around, but you stay together, etc. Have a "destination" to arrive at.
Write a story about the "adventure," where you will go and who/what you will see. Include parts about being in the car along time, and what they activities they did in the car, having healthy snacks from the cooler, etc. Start reading it to them every night. Change it up now and then, because you want them to be mentally prepared to be flexible (i.e., they arrived at the park, but this time it was raining, "oh no!"). It should always end happily no matter what, and try to include a sense of wonderment... leaving them curious and looking forward to adventures. Since you'll be visiting family, start showing them pictures and helping them learn names. Play at meeting those people, and how they should greet them, etc.
I recall from when my children were little that there were books out with some great ideas for trips like this. At one point, I bought a book with the states, so my children could follow along with where we were. It was designed for traveling with kids, you could map the route, etc. Look for a book with helpful ideas. One idea I remember from it was that I packed ahead of time little surprises. These came out in moments when the children had really tired of being in the car, were getting cranky, but had to wait a little longer before it was possible to stop. This was in the time period before DVDs, so I don't remember the other tips.
Just before the trip, they could help to pack their own small satchel (within reach) with comfort items, like others suggested. The night before the trip, they can help pack the cooler by putting carrots into baggies, etc.
Start taking day trips. Become a tourist in your own town, and keep increasing the distance to a reasonable amount (however long you'd expect them to be in the car without stopping, this summer). Afterwards, write text about the day trip, and let them draw a picture, even if the pic doesn't look like anything to you. Learn some travel games & practice them on your day trips. Your 4 yr old should be able to do that, & most 2 year olds can do some simple ones (i.e., find a green car, 2 dogs, etc.). Look for, or make a pictoral travel bingo game. Use these games when you want them to be a little attentive to some amazing scenery.
We now have a DVD player in the van, which is great most of the time, but it has had it's sad moments. i.e., when my teenagers have missed gorgeous scenery, or funny unexpected events we drove past, because they were engrossed in a DVD.
Yes, you can drive past an entire canyon & they'll miss it.
So, try to learn about the drive ahead, and actually aim to include games like travel bingo during times that you want them looking around. Just make sure they can actually see things from the car seat- if not this idea won't work as well.
Arrange for your 'helpers' ahead of time, as keeping track of 2 youngsters at a family reunion is tough. Also, think about what safety info you want them to know, & teach it. Happy travels!