A: Yes it can look good, and second, B: what exactly are you trying to make? and C: what other alternative are you thinking about? I'm asking so we can compare for your particular situation,

The quality depends, of course, on drawing skills. But also about the chosen style and consistency of the graphical content. When chosing sprites, don't expect to make photo-realistic graphics. For cartoonish graphics though, it can work out really well. In facts, making your world, characters and animations look cartoonish, is easier to achieve with sprites. Because the shapes are more curvy / organic compared with polygon objects, and you have more freedom with the animations. Not that its impossible to do with 3D, but that requires high skills.

Speaking of skills, when chosing 3D, the overall difficulty to make things look *good* is higher. So unless you have plenty of time to create a "next-gen" engine + the artists that can make the content, a 3D engine will quickly look outdated when people compare it to Crysis, Unreal, or whatever we got. This is less of a problem when going for 2D. At least... if you can pick a specific, consistent style. And since you also aim for mobile devices, you can't make too complex 3D stuff anyway.

As for the technical aspect to make things look good, consider lighting as one of the most important factors. In 3D, there are a lot of options to simulate somewhat realistic lighting. Shadowmaps, geometric shapes, normal/specular mapping, (baked) GI, and so on. With sprites, this is a bit harder to achieve because your scene is literally flat, and thus lacking information you would need for proper lighting. Although a cartoonish style may not need realistic "correct" lighting, you still may need some tricks to get it look cool instead of flat and dull.

This is probably the reason why platform games are often semi-3D. Using a mixture of 3D shapes and sprites. Don't forget you can still use OpenGL for a 2D looking game. But as said, making a 3D engine requires more work in general. So if you don't really need it...

Greets,

Rick

A Tower Defense game. I would just make it 2D. Because you will likely reach your goal faster (= making the game), it likely runs better on mobile devices, and most important, drawing topview walking characters or towers likely looks better than using (low poly) 3D models. Just compare old RTS games (Command & Conquer, ...). I found the drawed sprite ones look better than their 3D counterparts. Because sprites can show any complex drawing, while with low-poly models, you are stuck to more simplistic shapes. Same with lighting & animations.

I don't know what you are using right now, but OpenGL can draw transparent quads (sprites) just as well. Neither are you forced to use all kinds of complex shaders or lights. In other words, with OpenGL, you can do what any 2D engine can do as well. So if you like the way how GL works, you can still decide to go for GL of course. And since GL works on those mobile devices as well, its not such a crazy choice.