Instead of trying to predict traffic levels and road construction delays ahead of time, I would plan of using Google Maps on your iPhone or Android after you get your rental car.
If the app shows longer travel time, with big stretches of "red" on I-4, then use SR-417, the Central Florida GreeneWay, despite the tolls.
I-4 (no tolls) and SR-417 (many tolls) are both just under 50 miles and just over 50 minutes from Orlando-Sanford Airport to Epcot (to pick an arbitrary, central location at WDW) -- without traffic. Plan on around a hour to a WDW resort hotel.
I-4 is sometimes seriously overloaded with cars. And I-4 is undergoing a huge, multi-year improvement project. This can add significant time and aggravation. But if the traffic is moving well most of the way, it's a good route and it saves money.
If you're not using a SunPass transponder, you have plan on a number of toll plazas on SR-417. If they're backed up, that can add time and aggravation on that route.
By the way, if you use SR-417, you might as well stay on it until Exit 6, World Center Drive (which becomes Epcot Center Drive). Google Maps sometimes want you to cut over to I-4 on one of the east-west roads.
On more thing, even if you decide to use I-4, your GPS or map app will probably direct you to use a toll road between Sanford Airport and I-4. You can avoid this, if you want, by changing settings on your GPS or map app.
Hard to say which route is faster. SR417 will cost around $8 in tolls and is a "circular" route to the east. I4 is a more direct route but it's either city surface roads to get to I4 (Lake Mary Blvd) or back track up SR417 to I4 from the airport. That will cost you maybe $.75 in tolls.
Time of day matters on I4, no matter what day of the week. When I worked for Disney and has a night shift, the area around Kirkman was almost always backed up in the 2-3pm time frame on Sat and Sun. Now with the construction, it's a crap shoot. Waze is going to be your friend (or any other GPS with real time traffic).
Remember I-4 is under construction for the next 5 years to add two additional lanes both ways. The construction is from Disney to the north side of Orlando.