Yes. Pretty much.
Any defense with the right personnel and good scheme can defend the spread, but if I were to choose a defense with the spread in mind it would be the 4-2 or 3-3. If you remove the traditional gap responsibility and alignment from a 4-3, it would be pretty serviceable as well. The more that you remove gap responsibility and have players work inside- out against the front side of RPO you are going to be in a lot better shape. RPO teams are good at isolating the back side end, linebacker and a safety depending on how they run it. The 4-3 and 3-4 concepts on the scheme side of give a way ton of pre-snap tells, and the 4-2 and 3-3 effectively eliminate those tells. The reason is by committing to a six man box rather than a 7, you can effectively balance your defense without sliding.
The scheme makes the back side safety a second level run defender from depth and what traditional 2 high systems do is make it pretty evident based upon FS/WLB alignment precisely how you intend to cover the slot. The more you can mask your pre-snap coverage and alignment, it makes it hard to for the QB where they want to run their bubble or snag concept type route to.
Inside the box, because the LB's are flow players rather than gap alignment you get better pursuit to the front side of zone, you can get away by sending pressure to one side or the other and not leave gaping holes in the middle of your run defense. If you are running 4-3 cover 2 pressure against RPO you can't really send pressure off the edge without pre-snap indicating that your coming. Takes too long and the RPO concept is a 60's (quick set, zone) rather than a long 5 step type drop action. So you have to cheat it to bring an OLB, whereas in the 4-2 or 3-3 just because of alignment and personnel decisions you can bring pressure from just about anywhere and not immediately by alignment give away what you are doing behind it because you could be man to one side, zone to the other, or a number of combos. Most of the time we were 2/1 coverage, but with the 4-3 unless you abandon the 2 high, you are going to have to show you are running a zero/one concept.
Hope that makes sense.