If you are traveling between the Northeast and the Chicago area, the toll roads are generally the fastest and most direct. However, there are some very good alternatives - but you do have to balance off time and extra miles with additional fuel costs.
From the DC/Baltimore area, taking I-270/I-70 to the PA Turnpike and on to the Ohio Turnpike and Indiana Toll Road is fastest. A great alternate is I-70/I-68/I-79/I-70 to Indy - then I-65 to Chicago (or if you are going past Chicago into Wisconsin, take I-74 to I-39, or if you want to get to I-80 to go west, stay on I-74 to I-80). Note that US-40 is a "shortcut" from I-68 back to I-70. It's considerably shorter, but it's about 30 minutes longer. It makes up for that by being quite scenic and it goes through some very historical towns.
From Philly and parts of NJ, you can get out to King of Prussia and take US-422 to Reading, then PA-183 to I-78 (or take I-78 all the way from NJ). From there, you can take I-78 and I-81 to I-70 and follow the previous route. Another option from I-78 is US-322 north out of Harrisburg to State College to pick up I-80. US-322 is expressway most of the way. Also, if you are coming in I-78 from NJ, you can use PA-33 to get to I-80. I-80 is a good route from northern NJ.
From I-80, you can take I-76 through Akron to I-71, then US-30 across Ohio and Indiana. It's now a full expressway across Ohio and a good 4 lane with some traffic lights across Indiana. However, if you go that way, I'd advise you not to take US-30 west of I-65, it becomes VERY congested. Take I-65 back to I-80.
From New England, your best alternative to I-90 (Mass Pike, NY Thruway) is I-84 through Hartford to Scranton to I-81 to I-80 (or farther south if you are heading for I-70, follow previous recommendation to avoid the PA Turnpike).
From the Albany area, take I-88 to Binghamton, then I-81 south to I-80 or points south - or take I-86/NY-17 back to I-90 to I-271 around Cleveland to I-71. You can take US-30 or stay on I-71 to Columbus to pick up I-70.